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Salvia miltiorrhiza: Chemical and pharmacological review of a medicinal plant
Abstract
Salvia miltiorrhiza is a well-known traditional Chinese herb, belongs to the family of Labiatae, is used in many parts of the world to treat various conditions due to their excellent medicinal values. It is rich sources of tanshinone I, tanshinone II, miltirone and salvianolic acid and a wide range of chemical compounds. Extracts of the plant, particularly those from the root, possess useful pharmacological activities. Particular attention has been given to anti-oxidant activity, anti-microbial activity, antivirus activity, anti-cancer, anti-inflammatory, cardiovascular disease and so on. An account of chemical constituents and biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of S. miltiorrhiza. The aim of this review is to up-date and to present a comprehensive analysis of traditional uses, pharmacological reports and phyto-constituents isolated from the plant.
... It grows well in its natural habitat on hillsides, meadows, and grassy areas next to streams and forest edges. Danshen adapts to both sunlight and partial shade, and grows best in soil that is rich and damp but drains well, especially if it is sandy [3]. Danshen is used as a raw material for making traditional Chinese medicines [4], and it has a long history of use [3]. ...
... Danshen adapts to both sunlight and partial shade, and grows best in soil that is rich and damp but drains well, especially if it is sandy [3]. Danshen is used as a raw material for making traditional Chinese medicines [4], and it has a long history of use [3]. Research investigations have demonstrated that tanshinone I, tanshinone IIA, cryptotanshinone, and salvianolic acid B are primary bioactive constituents in danshen [5,6]. ...
... Research investigations have demonstrated that tanshinone I, tanshinone IIA, cryptotanshinone, and salvianolic acid B are primary bioactive constituents in danshen [5,6]. These compounds are believed to have antioxidant, anti-inflammatory, and cardiovascular protective effects [3,7,8]. They have been used to support heart health, promote blood circulation, and alleviate conditions like angina, high blood pressure, and certain types of strokes [9,10]. ...
Danshen (Salvia miltiorrhiza) is a perennial medicinal plant belonging to the Lamiaceae family. It is adapted to a wide range of soil pH with the potential to serve as an alternative crop in the United States. To enhance its cultivation and economic viability, it is crucial to develop production practices that maximize bioactive compound yields for danshen. The objective of this study was to investigate the effects of different harvest times on plant growth and subsequent yields of bioactive components of danshen. Three harvest times were selected (60, 120, or 180 days after transplanting [DAT]). In general, plants harvested at 180 DAT had higher plant growth index (PGI), shoot number, shoot weight, root number, maximum root length, maximum root diameter, and root weight compared to plants harvested at 60 or 120 DAT. However, plants harvested at 60 or 120 DAT had higher SPAD (Soil Plant Analysis Development) values. Plants harvested at 120 or 180 DAT had a higher content of tanshinone I, tanshinone IIA, cryptotanshinone, and salvianolic acid B compared to those harvested at 60 DAT. This study provides insights for optimizing the time of harvest of danshen to maximize plant growth and bioactive compound production.
... Danshen is an herbaceous perennial plant. In its natural environment, danshen grows on hillsides, meadows, and grassy places along stream banks and forest margins, between elevations of 90-1200 m [2]. Danshen prefers full sun to light shade, a rich, moist, and well-drained light sandy soil, and is naturally distributed in parts of Japan and China. ...
... It is cold hardy to approximately −10 • C, and can grow in USDA hardiness zones 5-9 [3]. The plant is multi-branched and can reach between 30-60 cm in height with a similar spread, producing blue-purple or white floral spikes extending about 30 cm above the foliage [2,4]. Danshen contains a variety of chemical components, which are mainly divided into two categories: one is the lipid-soluble component dominated by tanshinone diterpenes, and the other is the water-soluble component dominated by phenolic acid [5]. ...
... These major compounds in danshen resulted in its antioxidant, anti-microbial, anti-virus, anti-cancer, and anti-inflammatory properties. Therefore, danshen has been widely used to prevent and treat cardiovascular diseases [2]. ...
Salvia miltiorrhiza B., an herb used in traditional Chinese medicine, has been widely used to prevent and treat cardiovascular and other diseases. Currently, the majority of medicinal plants used in the US are imported from foreign countries, which involves transportation, quality control, and other issues. The objective of this study was to investigate the effect of nitrogen fertilization on growth and content of tanshinone I, tanshinone IIA, cryptotanshinone, and salvianolic acid B for Salvia miltiorrhiza B. in Mississippi. Plants were fertilized with one of five nitrogen (N) rates (0, 2, 4, 6, or 8 g N/plant from NH4NO3). Plants were harvested in November 2020 and 2021. Plants treated with 8 g N had higher plant growth index, leaf SPAD value, shoot and root number, shoot and root weight, maximum root length and diameter, shoot: root ratio, N concentration in root, and content of bioactive components compared to plants treated with 0, 2, 4 g N. Plants receiving 6 g N had similar shoot number, maximum root length, maximum root diameter, root weight and content of bioactive components compared to plants receiving 8 g N. However, plants receiving 6 g N had higher photosynthetic activity compared to plants receiving the higher N rate. Higher N rates increased plant growth and content of tested bioactive compounds.
... It has been medicinally used singly or together with other herbs in treating heart and vascular diseases, Alzheimer's disease, and blood clotting abnormalities. This is due to the possession of pharmacologically important compounds, which include salvianolic acids, diterpenoid, and tanshinones [50,51]. Furthermore, Danshen has been shown to reduce the production of LPS-induced NO, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) in RAW264.7 cells in a dose-response manner, both individually and in synergy with Notoginseng radix (Sanqi) [52]. ...
... Furthermore, Danshen has been shown to reduce the production of LPS-induced NO, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) in RAW264.7 cells in a dose-response manner, both individually and in synergy with Notoginseng radix (Sanqi) [52]. Four novel and fourteen reported compounds isolated and purified from S. miltiorrhiza were reported to exhibit anti-inflammatory activities with compound 4 (ethyl (2S,3R)-2-(3,4-dihydroxyphenyl)-4-((E)-3-ethoxy-3oxoprop-1-en-1-yl)-7-hydroxy-2,3dihydrobenzofuran-3carboxylate) demonstrating great suppression of secreted NO, TNF-α and IL-6 in LPSinduced RAW264.7 cells as well as decreasing the protein expression of iNOs and COX-2 [50]. ...
... salvianolic acids, diterpenoid and tanshinones Exhibits anti-inflammatory activities: by suppressing the secretion of NO, TNF-α and IL-6 and downregulates expression of iNOs and COX-2 [50][51][52]. ...
COVID-19 is a global pandemic that has claimed over 6,000,000 deaths since its appearance in late 2019. It is caused by the virus SARS-CoV2. In severe COVID-19 patients, the transition to ARDS is primarily due to cytokine storm, which is characterised by excessive inflammatory response and elevated levels of ferritin and pro-inflammatory cytokines in the serum, infiltration of neutrophils and monocytes into the lung; and reduced viral inhibiting cytokines, all of which contribute to the severity of the disease leading to death. The focus of this review is on the collation of medicinal plants with strong anti-inflammatory activities, which could be used alone or synergistically for enhanced therapeutic effect to cushion cytokine storm damaging effects. The plants collated evidently show by in vitro and in vivo analysis strong anti-inflammatory effects via suppression of Interleukin-8, Interleukin-6, Interleukin-1α, Interleukin-1β, Tumor Necrosis Factor-α, Interferon-γ, monocyte chemo-attractant protein-1, and nuclear factor kappa B (NF-κB) expression, in addition to inhibiting cyclooxygenase I and II (COX I and II), and inducible nitric oxide synthase (iNOS) activity. The medicinal plants collated in this review could be used alone or synergistically in the future in clinics for enhanced therapeutic effects to cushion cytokine storm damaging effects. Isolation of the active principle and studies of the specific mechanism of action of the plants could be the objectives of future research.
... It is well documented that S. miltiorrhiza plant is native to Japan and China (Wang 2010). This herb is highly valued for its roots that contain active ingredients such as tanshinones and miltirone diterpene compounds (Abenavoli et al. 2009;Wang 2010). ...
... It is well documented that S. miltiorrhiza plant is native to Japan and China (Wang 2010). This herb is highly valued for its roots that contain active ingredients such as tanshinones and miltirone diterpene compounds (Abenavoli et al. 2009;Wang 2010). Noteworthy, more than 70 ingredients were isolated from the roots of this plant (Wang 2010). ...
... This herb is highly valued for its roots that contain active ingredients such as tanshinones and miltirone diterpene compounds (Abenavoli et al. 2009;Wang 2010). Noteworthy, more than 70 ingredients were isolated from the roots of this plant (Wang 2010). ...
... Four of the best top 20 compounds (DHIT I, DHT I, tanshinone I and cryptotanshinone) are diterpenoid quinones found in the Chinese medicinal herb Danshen (Salvia miltiorrhiza) [72]. Six other compounds in the library (baicalin, danshensu, rosmarinic acid, salvianolic acid, stigmasterol and ursolic acid) are also found in Danshen [72], but offered little to no protection against oxytosis/ferroptosis in HT22 cells. ...
... Four of the best top 20 compounds (DHIT I, DHT I, tanshinone I and cryptotanshinone) are diterpenoid quinones found in the Chinese medicinal herb Danshen (Salvia miltiorrhiza) [72]. Six other compounds in the library (baicalin, danshensu, rosmarinic acid, salvianolic acid, stigmasterol and ursolic acid) are also found in Danshen [72], but offered little to no protection against oxytosis/ferroptosis in HT22 cells. Danshen, a perennial herb native to China, has been traditionally used for centuries to treat cardiovascular diseases [73], but its bioactive constituents possess a variety of pharmacological activities including anti-tumor, anti-oxidant, anti-microbial, anti-viral and anti-inflammatory activities [72]. ...
... Six other compounds in the library (baicalin, danshensu, rosmarinic acid, salvianolic acid, stigmasterol and ursolic acid) are also found in Danshen [72], but offered little to no protection against oxytosis/ferroptosis in HT22 cells. Danshen, a perennial herb native to China, has been traditionally used for centuries to treat cardiovascular diseases [73], but its bioactive constituents possess a variety of pharmacological activities including anti-tumor, anti-oxidant, anti-microbial, anti-viral and anti-inflammatory activities [72]. Importantly, Danshen and several of its constituents have been tested in cellular and animal models of AD and found to be neuroprotective [74,75]. ...
Because old age is the greatest risk factor for Alzheimer's disease (AD), it is critical to target the pathological events that link aging to AD in order to develop an efficient treatment that acts upon the primary causes of the disease. One such event might be the activation of oxytosis/ferroptosis, a unique cell death mechanism characterized by mitochondrial dysfunction and lethal lipid peroxidation. Here, a comprehensive library of >900 natural compounds was screened for protection against oxytosis/ferroptosis in nerve cells with the goal of better understanding the chemical nature of inhibitors of oxytosis/ferroptosis. Although the compounds tested spanned structurally diverse chemical classes from animal, microbial, plant and synthetic origins, a small set of very potent anti-oxytotic/ferroptotic compounds was identified that was highly enriched in plant quinones. The ability of these compounds to protect against oxytosis/ferroptosis strongly correlated with their ability to protect against in vitro ischemia and intracellular amyloid-beta toxicity in nerve cells, indicating that aspects of oxytosis/ferroptosis also underly other toxicities that are relevant to AD. Importantly, the anti-oxytotic/ferroptotic character of the quinone compounds relied on their capacity to target and directly prevent lipid peroxidation in a manner that required the reducing activity of cellular redox enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1). Because some of the compounds increased the production of total reactive oxygen species while decreasing lipid peroxidation, it appears that the pro-oxidant character of a compound can coexist with an inhibitory effect on lipid peroxidation and, consequently, still prevent oxytosis/ferroptosis. These findings have significant implications for the understanding of oxytosis/ferroptosis and open new approaches to the development of future neurotherapies.
... Salvia miltiorrhiza is known as Danshen in China. It is mainly used to treat cardiovascular diseases, cerebrovascular diseases, neurodegenerative diseases, blood circulation disorders, liver fibrosis and cancers (Wang, 2010). Salvia miltiorrhiza is composed of a high level of phenolic acid; salvianolic acid B and rosmarinic acid, the main active compounds that exhibit strong antioxidant activities and free radical scavenging effects which can be found in its roots and leaves (Zhang et al., 2010). ...
... The presence of alkaloids, triterpenoids and triple sugars could only be found in methanol and hexane but not in the water extract of the plant (Vijayalakshmi and Rao, 2020). Meanwhile, S. miltiorrhiza consisted of several bioactive compounds such as tanshinones, salvianolic acid A and salvianolic acid B (Wang, 2010). These bioactive compounds would contribute to the strong antioxidant properties in the plant. ...
Chinese herbal plants are known to be among the promising sources of variety of essential nutrients and antioxidant constituents. The objective of this study was to evaluate four Chinese herbs from the family of Lamiaceae which are popular in Malaysia; Plectranthus amboinicus, Vitex negundo, Salvia miltiorrhiza and Scutellaria baicalensis, on their proximate compositions, total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activities; DPPH and FRAP assays. Results showed that these herbs were relatively significant different from each other for their proximate compositions, TPC, TFC and antioxidant activities. Apparently, P. amboinicus has higher levels of ash (21.46±0.16%) and dietary fibre (41.24±1.25%) while V. negundo contained the highest crude fibre (19.41±1.98%) than the rest of the samples. Salvia miltiorrhiza consisted of high TPC (105.90±3.37 mg GAE/g), TFC (241.55±55.15 mg QE/g), DPPH radical scavenging activities (IC50: 169.10±14.17 µg/mL) and FRAP (103.09±2.84 µg FeSO4/g). Overall, the imported herb of S. miltiorrhiza is a potent natural antioxidant source with extremely low fat content to fight against oxidative stress and reactive oxygen species. More studies on the Lamiaceae family plant should be performed to determine more potential bioactivity which is beneficial to human health.
... In S. miltiorrhiza, the water-soluble ingredients have anticoagulation, cytoprotection, antiviral, antioxidation and other pharmacological effects [9]. The fat-soluble ingredients have antibacterial, anti-inflammatory, antitumor and other pharmacological effects [10,11]. Thus, the roots have been extensively used to treat inflammation, cardiovascular diseases, chronic renal failure, angina pectoris and dysmenorrhea in many regions in the world, mainly including Asia, Europe and the United States [2]. ...
... The previous research above indicated that jasmonates (JAs) could regulate Tans and phenolic acids biosynthesis. Meanwhile, previous studies showed that JA could regulate SalB content in S. miltiorrhiza through cross-talk with brassinolide, Ca 2+ , and H 2 O 2 [10,11]. A previous study displayed that JA participated in PGA regulating the antioxidant capacity of S. miltiorrhiza [47]. ...
Salvia miltiorrhiza Bunge is a traditional medicinal plant in China and poly-glutamic acid (PGA) is a valuable biopolymer. However, it is unclear whether PGA promotes growth and the accumulation of main medicinal components in S. miltiorrhiza. To elucidate this scientific question, the influences of PGA on the growth, physiological characteristics, and accumulation of main medicinal components in S. miltiorrhiza were explored through a pot experiment. The results revealed that PGA significantly promoted basal diameter, plant height, shoot and root biomass, as well as root volume, compared with control. PGA also increased SPAD value, net photosynthetic rate, actual and maximum photochemical efficiency of photosynthetic system II, photochemical quenching, and electronic transfer rate. Meanwhile, PGA increased transpiration rate, stomatal conductance, water use efficiency, leaf relative water content, and the contents of soluble protein, soluble sugar, and proline. Furthermore, PGA increased the activities of antioxidant enzymes and the contents of antioxidants. The above findings imply that PGA facilitated S. miltiorrhiza growth by enhancing photosynthetic performance, water metabolism, and antioxidant capacity. Additionally, PGA significantly improved the yield of rosmarinic acid, salvianolic acid B, dihydrotanshinone, cryptotanshinone, tanshinone I, and tanshinone ⅡA in roots by up-regulating the transcript levels of genes responsible for their biosynthesis. Our findings indicated that PGA promoted S. miltiorrhiza growth and the accumulation of main medicinal components in roots.
... 특히 단삼은 심혈관 질환에 효과가 있는 것으로 널리 알려 져 있으며 (Chen and Chen, 2017;Cheng, 2007;Li et al., 2018), 알츠하이머 증상 개선 (Chong et al., 2019;Hügel and Jackson, 2014;Zhang et al., 2016), 항골다공증 (Guo et al., 2014), 항당뇨 (Jia et al., 2019), 항염증 , 항산화 (Kang et al., 1997;Zhao et al., 2006) 등 다양한 질환과 증상에 효과가 있는 것으로 보고되었다. 또한 단삼에는 다양한 유효성분들이 존재하는데 대표적으로 탄시논 (tanshinone, Chang et al., 1990), 크립토탄시논 (cryptotanshinone, Li et al., 2021), 살비아놀산 (salvianolic acid) 과 로즈마린산 (rosmarinic acid) 및 밀티론 (miltirone) 등이 있다 (Wang, 2010). 이와 같이 단삼은 제약산업에서 활용될 수 있는 잠재력이 있으며 추후 국내에서 건강기능식품 및 건 강보조식품으로 개발될 수 있을 것으로 기대된다. ...
Background: Salvia miltiorrhiza Bunge, a medicinal plant belonging to the Lamiaceae family, is commonly used as a health-promoting tea in China. This study investigated and analyzed the improvements in S. miltiorrhiza growth, external quality, vegetation indices, and photosynthetic performance through photoperiod control. Methods and Results: The study was conducted with four different photoperiods: 8, 12, 16, and 24 hours of light period (h·d-1). The results showed that the 12 h·d-1 - 16 h·d-1 photoperiods were most effective for promoting shoot growth. This was determined by evaluating plant sizes, shoot biomass; various remote sensing vegetation indices including normalized difference vegetation index, photochemical reflectance index, and modified chlorophyll absorption ratio index; and five chlorophyll fluorescence parameters (Fv/Fm, ΦDo, ABS/RC, DIo/RC, and PIABS). Similarly, the root growth, root biomass, and external quality parameters (CIELAB color space values and visual score) indicated that a 12 h·d-1 - 16 h·d-1 photoperiod was the most effective. Conversely, continuous light conditions for 24 h·d-1 photoperiod significantly decreased most growth parameters and both shoot and root external qualities, suggesting inefficiency in such conditions. Conclusions: Therefore, the study recommends cultivating S. miltiorrhiza under a 12 h·d-1 - 16 h·d-1 range photoperiod to improve the growth, external qualities, and physiological characteristics.
... Salvia miltiorrhiza Bunge(danshen), a perennial herbaceous plant belonging to the Lamiaceae family, is one of the important medicinal materials widely used in traditional Chinese medicine preparations due to its diverse pharmacological effects (Wang 2010). Its dried roots and rhizomes are used as medicines (Cheng 2006). ...
Salvia miltiorrhiza is a kind of medicinal plant with various pharmacological activities. Few studies on the composition and diversity of rhizosphere microbial communities at different growth stages have been conducted on Salvia miltiorrhiz; in particular, salviorrhiza grows in soil that has been continuously planted for 3 years. The purpose of this study was to understand the changes of soil physicochemical properties of Salvia miltiorrhiza at different growth stages, and to study the composition and diversity of rhizosphere microbial community at different growth stages. Illumina NovaSeq sequencing technology was used to analyze the bacterial 16S rRNA gene and the fungal ITS region in the rhizosphere soil of Salvia miltiorrhiza at different growth stages. The results showed that the dominant bacterial phyla in the Salvia miltiorrhiza rhizosphere were Proteobacteria, Bacteroidetes, Acidobacteria, Firmicutes, Actinobacteria, and Chloroflexi. The dominant fungal phyla were Ascomycota, Mortierellomycota, Basidiomycota, and Rozellomycota. During the growth of Salvia miltiorrhiza, the physical and chemical properties of soil changed. As the Salvia miltiorrhiza grew, the content of available phosphorus, available potassium, pH, nitrate nitrogen, and ammonium nitrogen significantly decreased. Ammonium nitrogen and nitrate nitrogen had a greater impact on the bacterial community structure in the rhizosphere than on the fungal community structure. The work was to reveal differences in the rhizosphere bacterial and fungal community structure during different growth stages of Salvia miltiorrhiza, further understand the changes of rhizosphere microbial ecological characteristics and soil physicochemical properties during the cultivation of Salvia miltiorrhiza.
... It is native to China and Japan. In its native habitat, danshen commonly grows on hillsides, meadows, and grassy areas near streams and forest edges, typically at elevations between 90 and 1200 m [1]. Because of its critical bioactive components, including salvianolic acid B, cryptotanshinon, tanshinone I, and tanshinone IIA [2], it has aroused interest from the pharmaceutical industry. ...
Danshen (Salvia miltiorrhiza) is an herbaceous plant widely used in the pharmaceutical industry. However, the majority of medicinal plants utilized in the US are imported, posing challenges such as fluctuations in bioactive compound concentrations and insufficient supply to meet demand. Determining the optimal plant density is a key management decision for danshen production. This study aimed to investigate the effects of different plant densities on the growth and bioactive compound content of danshen cultivated in Mississippi. A field experiment was conducted to investigate the effects of different plant densities on individual plant growth, photosynthesis, and the content of bioactive components in danshen in 2020 and 2021. Six plant densities were designed: 30 × 20 cm (between row spacing × within row spacing), 30 × 30 cm, 30 × 40 cm, 45 × 20 cm, 45 × 30 cm, or 45 × 40 cm. A plant density of 45 × 40 cm resulted in danshen plants exhibiting the highest Plant Growth Index (PGI), SPAD, root number, shoot number, shoot fresh and dry weight, maximum root diameter, maximum root length, net photosynthesis, intracellular CO2 concentration, tanshinone I, and cryptotanshinone, regardless of year. Plants spaced at 45 × 30 cm had similar root fresh weight, root dry weight, and tanshinone IIA and salvianolic acid B levels compared with plants grown at the 45 × 40 cm spacing, and both were significantly higher than other densities.
... Traditional functional feature: Salvia miltiorrhiza, a member of the Lamiaceae family, with spreading stems and widely spaced leaves. It has been widely utilized to treat a variety of disorders [101] . Salvia miltiorrhiza is a well-known traditional Chinese herb from the Labiatae family that is used in many parts of the world to cure a variety of ailments due to its great medicinal properties have useful pharmacological activities. ...
... Flavonoids are among the phytoestrogens. It originally belongs to the 90-1200 meters' heights in Japan and China (23). Studies showed that flavonoids play an antioxidant role that may reduce oxidized LDL cholesterol and, on the other hand, inhibit platelet aggregation, improve endothelial function, and they also have an anti-inflammatory function (24,25). ...
Objectives: This study aimed to investigate the effect of Vitex agnus-castus (VAC), and Salvia officinalis extracts on serum lipids in postmenopausal women referred to the Bone Densitometry Center, Namazi Hospital, Shiraz, Iran. Materials and Methods: This randomized clinical trial was conducted on 89 postmenopausal women in 2016 using random permuted blocks with a block size of 3 in the three groups, including the VAC group (3.2-4.8 mg/q8h), S. officinalis group (100 mg/q8h), and placebo group for three months. Women were finally compared in terms of low-density lipoprotein, triglycerides (TG), and highdensity lipoprotein before and after the intervention. Data were analyzed using SPSS-16 software. Descriptive statistical tests and paired t test were used to compare the groups. Results: A significant decrease in serum cholesterol, low-density lipoprotein, and triglycerides levels and also increase in mean serum high-density lipoprotein levels were observed in VAC and S. officinalis groups before and after the intervention (P = 0.0001). In comparison, no significant change was observed in serum level of any lipoproteins in the placebo group. Conclusions: Considering the decrease in the level of cholesterol, low-density lipoprotein, triglycerides, and increased highdensity lipoprotein after using VAC and S. officinalis in this study, these herbs can be proposed as blood lipid-lowering agents in postmenopausal women.
... While lipophilic molecules include tanshinones I, IIA, IIB, V, VI, cryptotanshinone, salviol, and miltirone, hydrophilic substances consist of salvianolic acids A through E, rosmarinic acid, salvianolic acid G, and methyl rosmarinate. The principal bioactive components, phenolic acids, and diterpenoids exhibit diverse activities such as antioxidant, anti-inflammatory, cardioprotective, and anticancer effects Jia et al. 2019;Ngo et al. 2019;Shi et al. 2019;Wang 2010). ...
A variety of secondary metabolites or so-called phyto-metabolites with different biological properties and structures can be produced by medicinal plants and filamentous fungi. These secondary metabolites can be employed as toxins, dyes, medications, insecticides, etc. With the advent of the post-genomic era, an increasing number of enigmatic or unrecognized gene clusters responsible for the biosynthesis of secondary metabolites are being uncovered. The more thorough investigation of industrially significant secondary metabolites has, however, so far been constrained by the persistent absence of adaptable, reasonably easy-to-use, and highly effective genetic manipulation approaches. This conundrum might be resolved with the development of CRISPR/Cas9-based genome-editing technology, which has revolutionized genetic research and made it possible to use and discover new medicinal chemicals from plants and filamentous fungi. In this chapter, we offer a comprehensive overview of the CRISPR/Cas9 system and a concise recapitulation of the latest applications of genome editing achieved through CRISPR/Cas9. Including specific instances, we also provide a concise exploration of how the CRISPR/Cas9 system and CRISPRa have been employed to enhance secondary metabolite yields and discover new biologically active compounds. Moreover, we address challenges and constraints associated with utilizing CRISPR/Cas9 genome-editing technology in investigations related to secondary metabolite production. Additionally, we delve into potential applications of the CRISPR/Cas9 methodology in the context of medicinal plants and filamentous fungi.
... 단삼은 중국에서 약 2000년 전부터 사용되어져 왔으며 근대 에 들어 1953년에 공식적으로 중국약전(Chinese pharmacopoeia)에 기록되었을 뿐만 아니라 Guo et al., 2014;Wang et al., 2017), 2012년에는 대한민국약전(Korean pharmacopoeia)에도 기록되었다 (KFDA, 2012). 단삼은 탄시 논 I(tanshinone I), 밀티론(miltirone), 살비아놀산(salvianolic acid) 및 다양한 생리활성 화합물(bioactive compounds)의 풍 부한 공급원으로 활용 가능하며 (Wang, 2010), 특히 단삼의 추출물은 항산화 (Cao et al., 1996;Peng et al., 2019), 항미생물 (Zhao et al., 2011), 항바이러스 (Wu et al., 2007), 항암 (Franek et al., 2005;Dong et al., 2011;Jiang et al., 2017), 항염증 (Qi et al., 2019), 심혈관 질환 (Liu et al., 2016), 뇌세포 보호 (Zhang et al., 2009), 간세포 보호 (Yin et al., 2009) (Oh et al., 2022), 배추(Brassica rapa ssp. pekinensis) (Oh et al., 2014), 라디 치오(Cichorium intybus var. ...
Salvia miltiorrhiza is a medicinal crop belonging to the Lamiaceae family. It is commonly used in China as an ingredient in health-promoting teas that enhance immunity and prevent diseases. Although some Korean local farmers have reported that S. miltiorrhiza grows vigorously in high temperatures and produces roots with a deep red color, there is no clear evidence or literature to confirm this. Therefore, this study investigated the growth and external quality of S. miltiorrhiza in response to different day and night temperature levels. Day and night temperature treatments were designed into four levels: 20/15, 24/19, 28/23, and 32/27°C, respectively. Among the parameters related to plant sizes, the shoot height and number of roots showed the highest values in the 32/27°C treatment, while other parameters, particularly the shoot width and root length exhibited the highest values in the 28/23°C treatment. In contrast, the majority of parameters, including the fresh weight and dry weight, which are indicative of root biomass, were lowest in the 20/15°C treatment, suggesting that S. miltiorrhiza, a species that prefers relatively high temperatures, thrives in warmer conditions. Importantly, the root fresh and dry weights, which are likely to be correlated with the market value of S. miltiorrhiza, showed the same significance levels within the temperature range of 24/19–32/27°C, but not in the relatively low-temperature treatment of 20/15°C. Thus, cultivation of S. miltiorrhiza is deemed feasible within all temperature ranges except for 20/15°C, with optimal conditions falling within the temperature range of 24/19–32/27°C. The CIELAB a* value, associated with red color, was highest in the comprehensive assessment of the 32/27°C treatment. Moreover, in the 32/27°C treatment, the Royal Horticultural Society (RHS) color chart values were found to indicate a deep reddish or brown-red color, with readings of 166B and 174A. Additionally, the root color obtained the highest visual score in the 32/27°C treatment. Based on previous studies, a* is considered to be related to the content and quantities of tanshinones and other hydrophilic phenolic compounds, which are effective components associated with the orange-red color. Therefore, it is recommended to cultivate S. miltiorrhiza at a high temperature of 32/27°C to achieve high growth rates, excellent external quality, and produce superior S. miltiorrhiza plants.
... S. miltiorrhiza is an important Chinese medicinal material using dried roots and rhizomes as medicine, which has the effects of promoting blood circulation, regulating menstruation, sedating and tranquilizing, reducing swelling, and relieving pain [38]. Due to the single planting mode and the reasons for repeated cropping, the root rot of S. miltiorrhiza caused by Fusarium spp., which has become one of the main diseases, seriously threatened the safety and healthy development of S. miltiorrhiza industry [31]. ...
Root rot as a result of Salvia miltiorrhiza is a common root disease caused by Fusarium spp., which has become one of the main diseases affecting the production of S. miltiorrhiza. Currently, several hypovirulence-related mycoviruses have been identified in many phytopathogenic fungi, including Fusarium spp., which show potential as biological controls. In this study, we report a new mycovirus, Fusarium oxysporum partitivirus 1 (FoPV1), isolated from F. oxysporum strain FCR51, which is a causal agent of S. miltiorrhiza dry rot. The FoPV1 genome contains two double-stranded RNA segments (dsRNA1 and dsRNA2). The size of dsRNA1 is 1773 bp, and it encodes a putative RNA-dependent RNA polymerase (RdRp). The dsRNA2 is 1570 bp in length, encoding a putative capsid protein (CP). Multiple sequence alignments and phylogenetic analyses based on the amino acid sequences of the RdRp and the CP proteins indicated that FoPV1 appears to be a new member of the family Partitiviridae that is related to members of the genus Gammapartitivirus. Pathogenicity assay showed that FoPV1 confers hypervirulence to its host, F. oxysporum. This is the first report of a partitivirus infecting F. oxysporum and the first hypovirulence-related mycovirus from the causal agent of S. miltiorrhiza dry rot.
... Salvia miltiorrhiza, belonging to the family Lamiaceae, has roots that are medicinally used in the treatment of cardiovascular diseases and as antibacterial and anti-inflammatory agents. [20] ...
The liver is the main organ for metabolic and detoxification reactions in the body. Therefore, its diseases can be associated with both metabolic disorders, such as insulin resistance, obesity, diabetes, or dyslipidemia, and exogenous insults such as drugs, xenobiotics, or alcohol. Indeed, lifestyle changes are the primary approaches for the prevention and treatment of liver diseases. Since ancient times, herbals have also been used for preventive and therapeutic purposes, because of their anti-apoptotic, anti-inflammatory, and antioxi-dant effects. Here, the literature was reviewed for potential therapeutic effects of plants and their compounds by including in vitro and in vivo studies, as well as clinical trials. Although the available data imply some beneficial roles of herbals on the liver, the indications and posology of specific plants need to be clarified through multicenter, randomized clinical trials.
... Salvia miltiorrhiza, belonging to the family Lamiaceae, has roots that are medicinally used in the treatment of cardiovascular diseases and as antibacterial and anti-inflammatory agents. [20] ...
The liver is the main organ for metabolic and detoxification reactions in the body. Therefore, its diseases can be associated with both metabolic disorders, such as insulin resistance, obesity, diabetes, or dyslipidemia, and exogenous insults such as drugs, xenobiotics, or alcohol. Indeed, lifestyle changes are the primary approaches for the prevention and treatment of liver diseases. Since ancient times, herbals have also been used for preventive and therapeutic purposes, because of their anti-apoptotic, anti-inflammatory, and antioxidant effects. Here, the literature was reviewed for potential therapeutic effects of plants and their compounds by including in vitro and in vivo studies, as well as clinical trials. Although the available data imply some beneficial roles of herbals on the liver, the indications and posology of specific plants need to be clarified through multicenter, randomized clinical trials.
... Salvia miltiorrhiza is a perennial species native to Asian countries including China and Japan, which is very valuable in traditional Chinese medicine because of its roots (Danshen). The species grows at altitudes of 90-1200 m in grassy places and river banks (Wang 2010;Luo et al. 2023;Wei et al. 2023). Tanshinone and phenolic acids such as rosmarinic, caffeic, and salvianolic acid are the most important bioactive compounds of the plant, which have biological activities against some important human diseases (Ma et al. 2013;Deng et al. 2019;Fu et al. 2020;Mahalakshmi et al. 2021). ...
Salvia miltiorrhiza (Lamiaceae) is a medicinal plant rich in tanshinones and phenolic compounds, which have anticancer activity with positive effects on the cardiovascular system as well. The bioactive compounds are mainly biosynthesized and accumulated in the plant roots. Therefore, their production is of great interest in biotechnological systems, especially the hairy root cultures. In the present study, the growth curve of the superior hairy root lines (HRLs) induced by wild-type strains of Agrobacterium rhizogenes (C58, LBA, ATCC, and A4) was studied. The most significant biomass accumulation by the third week was observed in the HRL1 (4.80 ± 0.13 g) and HRL4 (3.98 ± 0.03 g). In order to increase the compounds, the selected line (HRL1), was treated with Zn nanoparticles (0, 50, and 100 mg/l), methyl jasmonate (0, 50, and 100 μM/l), and coronatine (0, 0.1, and 0.2 μM/l) at 24, 48, and 72 h. The highest fresh (3.45 ± 0.08 g) and dry (0.33 ± 0.00 g) weights of the root was found after 72 h in the medium without coronatine. The maximum content of tanshinone (7.30 ± 0.09 mg/g DW) and rosmarinic acid (8.01 ± 0.10 mg/g DW) were obtained in the hairy roots treated with 0.1 μM/l coronatine after 24 and 72 h, respectively. The greatest caffeic acid (6.83 ± 0.05 mg/g DW) and salvianolic acid B (2.56 ± 0.07 mg/g DW) content was found at 50 mg/l Zn nanoparticles after 72 h. The findings can be applied to increase the commercial production of these valuable bioactive compounds in large-scale cultures.
... Subsequent research has demonstrated the significant cardiovascular benefits of unrefined Salvia miltiorrhiza Bunge extracts, including coronary artery relaxation, myocardial antioxidant rescue, platelet aggregation inhibition, and the prevention of low-density lipoprotein oxidation. Additionally, these extracts have been shown to enhance the long-term memory retention in rodent models [40][41][42]. Furthermore, Salvia miltiorrhiza Bunge extracts have displayed anti-neoplastic properties across a range of human cancer cell types, such as gastric adenocarcinoma, prostate carcinoma, breast adenocarcinoma, colorectal carcinoma, and lung adenocarcinoma cells [43]. ...
Danshen, also known as Salvia miltiorrhiza, is a medicinal herb used in traditional Chinese medicine. Its potential impact on endometrial cancer has not been thoroughly investigated. This study aimed to examine the effect of dihydroisotanshinone I (DT), a compound found in Danshen, on the viability of ARK1 and ARK2 endometrial cancer cells and its mechanisms. The results showed that 10 μM DT inhibited cell viability of ARK1 and ARK2 cells by inducing apoptosis and ferroptosis, which was achieved by blocking the expression of GPX4. In vivo experiments using a xenograft nude mouse model indicated that DT treatment significantly reduced tumor volume without causing any adverse effects. These findings suggest that DT may be a potential therapeutic agent for inhibiting endometrial cancer cell viability, but further research is needed to confirm these results.
... They have antioxidant, antidiabetic, antibacterial, anticancer, antiplasmodial, and anti-inflammatory properties and are utilized in traditional medicine all over the world (Ulubelen, 2003;Kamatou et al., 2008). For instance, traditional Chinese medicine uses the endemic Chinese plant Salvia miltiorrhiza Bunge (also known as "Danshen"; Photo-table 1) to treat hyperlipidemia, cardiovascular and cerebrovascular illnesses, and other conditions (Wang, 2010). Salvia hispanica L., a crucial staple and therapeutic herb in Mesoamerica during pre-Columbian times, is today sold commercially as a "superfood" throughout the world (Ali et al., 2012). ...
This paper comprises a study of the plant lists of Salvia, as genus of plants from 11 subgenera in the mint family (Lamiaceae) grown in Zagreb Botanical Garden of the Faculty of Science since 1895 until 2022. Synonymy, nomenclature and origin of plant material have been sorted. Lists of species grown in the last 127 years have been constructed to show that during that period at least 126 taxa from the genus Salvia (2 from subgen. Audiberia, 40 from subgen. Calosphace, 6 from subgen. Glutinaria, 8 from subgen. "Heterosphace” (informal designation for this group), 2 from subgen. Perovskia, 2 from subgen. Rosmarinus, 18 from subgen. Salvia and 48 from subgen. Sclarea) inhabited the Garden’s collections. Today, the genus is represented by 61 taxa from 8 subgenera in Botanical Garden: 1 from subgen. Audiberia, 12 from subgen. Calosphace, 4 from subgen. Glutinaria, 4 from subgen. “Heterosphace”, 1 from subgen. Perovskia, 1 from subgen. Rosmarinus, 13 from subgen. Salvia and 25 from subgen. Sclarea.
... The hydrophilic and lipophilic substances were extracted from Salvia miltiorrhiza as biochemicals. Rosmaric acid, baicalin, and stigmasterol are some of the isolated hydrophilic compounds, while tanshinone I, salviol, and maltirone are some of the isolated lipophilic compounds [114]. In female ICR strain mice, oral administration of a mixture of S. miltiorrhiza with liquified calcium at dosages of 50, 100, and 200 mg/kg bw/day prevented bone deterioration brought on by a lack of oestrogen via blocking the RANKL signalling pathway. ...
Postmenopausal osteoporosis, an epidemic disorder is defined as a loss in bone mineral density and a greater possibility of fractures in older women. It is a multifactorial disease under the control of various genetic, hormonal, and environmental factors. Insufficiency of estrogen hormone, leads to postmenopausal osteoporosis. Hormone replacement therapy (HRT), despite being the most effective treatment, it is associated with the risk of breast cancer and cardiovascular disorders. This review seeks to compile the most recent information on medicinal plants and natural compounds used to treat and prevent postmenopausal osteoporosis. Furthermore, the origin, chemical constituents and the molecular mechanisms responsible for this therapeutic and preventive effect are also discussed. Literature research was conducted using PubMed, Science direct, Scopus, Web of Science, and Google Scholar. Different plant extracts and pure compounds exerts their antiosteoporotic activity by inhibition of RANKL and upregulation of OPG. RANKL signaling regulates osteoclast formation, characterized by increased bone turnover and osteoprotegrin is a decoy receptor for RANKL thereby preventing bone loss from excessive resorption. In addition, this review also includes the chemical structure of bioactive compounds acting on NFκB, TNF α, RUNX2. In conclusion, we propose that postmenopausal osteoporosis could be prevented or treated with herbal products.
... Previous studies indicate that Salviae miltiorrhizae Radix plays an essential role in the neuroprotective effect of GCD [23]. Salviae miltiorrhizae Radix (danshen), the dried root of Salvia miltiorrhiza BGE (Labiatae), is a very important TEAM that promotes blood flow to overcome blood stasis [24] and is currently used to treat cerebrovascular diseases, thrombosis, vasculitis, dysmenorrhea, postpartum abdominal pain, chest pain, and contusion in TEAM [25]. Previous studies suggest that Salviae miltiorrhizae Radix displays antiarteriosclerotic [26], anti-inflammatory [27], antidiabetic [28], antioxidant [29], antibacterial [30], anticancer [31], neuroprotective [32], immunomodulatory activity [33], antithrombotic, and antioxidant effects [34]. ...
Background:
Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD's effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content.
Methods:
The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography.
Results:
Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not.
Conclusions:
The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization.
... The genus is an economically important of the Lamiaceae family. For instance, Salvia miltiorrhiza, endemic to China, is a traditional Chinese medicine that is widely used to treat cardiovascular and cerebrovascular diseases and hyperlipidemia (Wang, 2010). The genus Salvia comprises approximately 1000 species worldwide (Alziar, 1988;Walker et al., 2004;Wei et al., 2015;Drew et al., 2017;Will, Classen-Bockhoff, 2017). ...
The high-mountain ecosystems of Central Asia consist of very rich biodiversity with unique plant communities and many endemic species. High human pressure and long drought periods due to global warming have caused habitat destruction in these areas and a parallel increase in the number of endangered species. In Uzbekistan, the number of red listed plant species has risen in the last 30 years, from 163 in 1984 to 324 in 2009. Among those red-listed species are 23 species in the Lamiaceae family. The aim of this study was to estimate the current populations of red-listed species Salvia submutica. This species is endemic to the Nuratau ridge, and it is growing under climatic changes and human pressure. We found two populations of this species in the Nuratau ridge. For each population, we measured the plant density and determined the population spectrum. We also describe the plant community where each population grew. At all sites, the population density was low, with most populations being classified as mature with centered ontogenetic structure. These results indicated this species might, in the near future, become extinct in the wild.
... Salvia miltiorrhiza, also known as red sage or Chinese sage, is one of the most widely used traditional herb medicines recommended for the treatment of a variety of diseases, such as cardiovascular diseases, hepatitis, hepatocirrhosis, chronic renal failure and dysmenorrhea. In S. miltiorrhiza, two pharmacologically active fractions were identified: lipophilic diterpenoids transhinones and water-soluble phenolic acids [16]. In recent years, research has been focused on the phenolic acid fraction where twenty-five phenolic acid compounds have been isolated and identified. ...
Salvianolic acid B (SalB) is a bioactive compound from Salviae miltiorrhizae, one of the most important traditional herbal medicines widely used in several countries for the treatment of cardiovascular diseases. The aim of this study was to evaluate the in vitro effect of SalB on the expression and the activity of matrix metalloproteinase 9 (MMP-9), a zinc-dependent proteolytic enzyme, in human MDA-MB-231 breast cancer cells. This cellular model is characterized by a marked invasive phenotype, supported by a high constitutive expression of MMPs, especially gelatinases. SalB was first of all evaluated by in silico approaches primarily aimed at predicting the main pharmacokinetic parameters. The most favorable interaction between the natural compound and MMP-9 was instead tested by molecular docking analysis that was subsequently verified by an enzymatic inhibition assay. MDA-MB-231 cells were treated with SalB 5 µM and 50 µM for 24 h and 48 h. The conditioned media obtained from treated cells were then analyzed by gelatin zymography and reverse zymography to, respectively, evaluate the MMP-9 activity and the presence of TIMP-1. The expression of the enzyme was then evaluated by Western blot on conditioned media and by analysis of transcripts through reverse transcriptase-polymerase chain reaction (RT-PCR). The in silico approach showed the ability of SalB to interact with the catalytic zinc ion of the enzyme, with a plausible competitive mode of action. The analysis of conditioned culture media showed a reduction in MMP-9 activity and the concomitant decrease in the enzyme concentration, partially confirmed by analysis of transcripts. SalB showed the ability to modulate the function of MMP-9 in MDA-MB-231 cells. To our knowledge, this is the first time in which the role of SalB on MMP-9 in a highly invasive cellular model is investigated. The obtained results impose further and more specific evaluations in order to obtain a better understanding of the biochemical mechanisms that regulate the interaction between this natural compound and the MMP-9.
... In Japan, you may buy Danshen items to improve your circulation and get rid of "blood stasis." The largest market for danshen is China, where it was valued more than US$120 million in 2002 6 . In China, you may get danshen in many different medicinal preparations. ...
Many factors contribute to CVD, however atherosclerosis and high blood pressure are major contributors. In addition, even in asymptomatic healthy individuals, ageing brings about a variety of morphological and physiological changes that have an impact on cardiovascular function and raise the risk of CVD. In some high-income nations, cardiovascular mortality rates have fallen since the 1970s, despite the fact that cardiovascular disease remains the leading cause of death globally. Natural products containing spiroketals have been identified in many different forms throughout the years, however molecules belonging to this class that have aryl rings fused to the spiroketal moiety are very rare. Some of the chemical components in the Compound Danshen Formula (CDF) have been demonstrated to have considerable pharmacological effect. The CDF is a mixture of three plants. OBioavail 1.1, a robust in silico model, was developed in our previous studies to estimate the oral bioavailability of compounds in humans by combining metabolic data. The human oral bioavailability of a collection of 805 structurally diverse pharmacological and drug-like substances were used to develop the model. It's safe to assume that Danshen's medications have earned a solid reputation in China for their ability to remedy heart problems. The impacts on blood flow and "blood stasis" are discussed at length in traditional Chinese medical books. TCM takes a more holistic approach than conventional medicine to fixing health problems in people. In contrast, deciphering the molecular processes of TCM would be exceedingly difficult because to the complexity of the chemical components and their activity in vivo.
... 13 The scarce resource of S. miltiorrhiza, as well as dissatisfactory yield and purity of DSS, limit the natural plant extraction of DSS to meet industrial requirement. 14 Therefore, chemical synthesis routes with classical Knoevenagel condensation 15 and Darzens condensation 16 gradually advance as alternative methods for DSS production. Although chemical synthesis approaches ease the limitation of S. miltiorrhiza, problems of poor chiral selectivity and laborious steps are inextricable. ...
Danshensu (DSS), a traditional Chinese medicine, is widely used for the treatment of cardiovascular and cancer diseases. Here, a one-pot multi-enzyme cascade pathway was designed for DSS synthesis from l-DOPA using tyrosine aminotransferase from Escherichia coli (EcTyrB) and d-isomer-specific 2-hydroxyacid dehydrogenase from Lactobacillus frumenti (LfD2-HDH). Glutamate dehydrogenase from Clostridium difficile (CdgluD) was also introduced for a self-sufficient system of α-ketoglutaric acid and NADH. Under optimal conditions (35 °C, pH 7.0, EcTyrB:LfD2-HDH:CdgluD = 3:2:1, glutamate:NAD+ = 1:1), 98.3% yield (at 20 mM l-DOPA) and space-time yield of 6.61 g L-1 h-1 (at 40 mM l-DOPA) were achieved. Decreased yields of DSS at elevated l-DOPA concentrations (100 mM) could be attributed to an inhibited CdgluD activity caused by NH4+ accumulation. This developed multi-enzyme cascade pathway (including EcTyrB, LfD2-HDH, and CdgluD) provides an efficient and sustainable approach for the production of DSS from l-DOPA.
... S. miltiorrhiza belongs to the family Lamiaceae and has been used widely in many countries, such as China, Japan, Korea and other Asian countries, to treat heart diseases, particularly myocardial infarction and angina pectoris [44]. There are two major classes of active compounds in S. miltiorrhiza (hydrophilic salvinolic acid and lipophilic tanshinones), both of which exhibit antiviral, antioxidant, anti-inflammatory and anti-HIV properties [75][76][77]. Lee et al. [78] showed that the aqueous extract of this plant had a protective effect in BALB/c mice against influenza virus by upsetting the viral replication or inhibiting the viral infection, leading to an antiviral state in the lungs. Hence, S. miltiorrhiza aqueous extract, as an orally active antiviral agent, could be used for prophylactic treatments against influenza. ...
At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for the development of anti-SARS drugs. Online search engines, such as Web of Science, Google Scholar, Scopus and PubMed, were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CLpro. Various pure compounds, including polyphenols, terpenoids, chalcones, alkaloids, biflavonoids, flavanones, anthraquinones and glycosides, have shown potent inhibition of SARS-CoV-2 3CLpro activity with 50% inhibitory concentration (IC50) values ranging from 2-44 µg/mL. Interestingly, most of these active compounds, including xanthoangelol E (isolated from Angelica keiskei), dieckol 1 (isolated from Ecklonia cava), amentoflavone (isolated from Torreya nucifera), celastrol, pristimerin, tingenone and iguesterin (isolated from Tripterygium regelii), tannic acid (isolated from Camellia sinensis), and theaflavin-3,3'-digallate, 3-isotheaflav1in-3 gallate and dihydrotanshinone I (isolated from Salvia miltiorrhiza), had IC50 values of less than 15 µg/mL. Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive, with Ki values ranging from 2.4-43.8 μmol/L. Given the significance of plant-based compounds and the many promising results obtained, there is still need to explore the phytochemical and mechanistic potentials of plants and their products. These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.
... Medicinal plants and food are commonly recommended as sources of natural antioxidants to reduce the risk of cardiovascular diseases, and their efficacy has been proven in clinical trials [22][23][24][25][26]. According to NIH, compared with artificial antioxidants, the antioxidant ingredients in natural plants and food are not a single compound but might work together to achieve antioxidant activity. ...
The rising prevalence of chronic metabolic disorders, such as obesity and type 2 diabetes, most notably associated with cardiovascular diseases, has emerged as a major global health concern. Reactive oxygen species (ROS) play physiological functions by maintaining normal cellular redox signaling. By contrast, a disturbed balance occurring between ROS production and detoxification of reactive intermediates results in excessive oxidative stress. Oxidative stress is a critical mediator of endothelial dysfunction in obesity and diabetes. Under a hyperglycemic condition, the antioxidant enzymes are downregulated, resulting in an increased generation of ROS. Increases in ROS lead to impairment of endothelium-dependent vasodilatations by reducing NO bioavailability. Chronic treatments with antioxidants were reported to prevent the development of endothelial dysfunction in diabetic patients and animals; however, the beneficial effects of antioxidant treatment in combating vascular complications in diabetes remain controversial as antioxidants do not always reverse endothelial dysfunction in clinical settings. In this review, we summarize the latest progress in research focused on the role of ROS in vascular complications of diabetes and the antioxidant properties of bioactive compounds from medicinal plants and food in animal experiments and clinical studies to provide insights for the development of therapeutic strategies.
... Drymosphace are importance of medical value, with Salvia miltiorrhiza being most widely used. "Danshen", a famous traditional Chinese medicine originating from the dried roots of S. miltiorrhiza, has been extensively applied to treat coronary heart diseases and cerebrovascular diseases [17]. Due to mass market demand, the wild resource of S. miltiorrhiza has reduced sharply. ...
Sect. Drymosphace is one of eight sections of Salvia subg. Glutinaria and includes 13 species and one dubious species that hold great economic value. Although the section is well supported, interspecific relationships remain unresolved. Moreover, most of this section’s plastome information remains unknown. In this study, we sequenced and assembled eight sect. Drymosphace plastomes and conducted comparative analyses within this section. The length of plastid genome sequences ranged from 151,330 bp to 151,614 bp, with 80 protein-coding, 30 tRNA, and four rRNA genes being annotated. The plastomes were found to be as conservative as other Lamiaceae species, showing high consistency and similarity in terms of gene content, order, and structure. Within the sect. Drymosphace, single-copy regions were more variable than IR regions, and the intergenic regions were more variable than the coding regions; nine hypervariable regions were detected, and some of them may be useful for the phylogenetic analysis of Salvia. The topologies inferred from all of the data sets indicated that sect. Drymosphace was monophyletic and that S. honania was sister to S. meiliensis. Compared to previous studies involving more sect. Drymosphace species, phylogenomic analyses can improve the phylogenetic resolution considerably.
... These pharmacological activities include the ability to elicit anti-oxidative, anti-cancer, anti-inflammatory, and anti-microbial effects, as well as the ability to promote blood circulation (Pang et al., 2016). Over the years, S. miltiorrhizae has been developed into over 30 medication formulations to treat CVDs, pneumonia, hyperlipidemia, and chronic nephritis (Wang, 2010). ...
Cardiovascular disease (CVD) and its associated risk factors have been ranked the number 1 cause of mortality in non-communicable diseases worldwide and Malaysia. The high statistic in CVD mortality indicates gaps and limitations in current treatment strategies using long-term drug prescription therapies. Hence, an immediate quest for alternative and effective treatments is needed. Medicinal herbs, which are ethnopharmacologically used to treat a wide range of conditions, have been used as an alternative or supplementary treatment for CVDs and their associated risk factors. The roots of Salviae miltiorrhizae have been traditionally used for centuries to treat various diseases including neurological disorders, cancer, and even coronary heart disease. Increasing evidence demonstrated a pharmacological basis for the action of S. miltiorrhizae and its active compounds, suggesting its potential in treating CVD. The objectives of this review were first to summarize published literature and synthesize the new body of knowledge on the use of S. miltiorrhizae as the potential medicinal herb that will positively impact the cardiovascular system, and secondly to elucidate the underlying mechanisms involved in promoting cardiovascular health. It is hoped that identification of key regulatory pathways by lipophilic and hydrophilic active compounds from S. miltiorrhizae will aid further investigation of its safety and efficacy to promote the use of evidence-based traditional medicinal herbs in alleviating symptoms and improve the prognosis of CVDs and their associated risk factors.
... Two classes of main active substances in S. miltiorrhiza, namely. lipophilic tanshinones and hydrophilic salvianolic acidsand both compounds have been found to have antioxidant, anti-inflammatory and antiviral properties (118). Huang and colleagues isolated two potent non-toxic HIV-1 intergrase inhibitors from this plant, which were derivatives of salvianolid acid: lithospermic acid and lithospermic acid B (119). ...
As the number of viral infections and in particular resistant viral strains increasing, existing remedies need to be improved and brought into line with the discovery of new antiviral agents to fight persistent viral infections. It is generally believed that the gene pool of medicinal plants is valuable and endowed with precious compounds to treat metabolic and infectious disorders. The purpose of this review is to gather the facts and investigate into the therapeutic potential of medicinal plants, herbs and spices in the administration of various viral diseases. COVID-19 infections are treated with available antiviral therapy with unsatisfactory clinical results. Persistent viral infections that are resistant to the available antivirals are terrifying threats and a serious health problem like influenza infection. SARS CoV 2 remains a major threat to animal and human health, which urgently requires effective antivirals. Due to the increasing frequency of viral infections and particularly resistant viral strains, the available therapeutic facilities must be improved, compensated by the discovery of new antiviral agents to fight against refractory viral infections. The treatment of herbal remedies as readily available alternatives for their compatibility with the body and fewer side effects compared to synthetic chemical treatments has become popular worldwide. Introduction:
... It has been used to treat and prevent cardio-vascular disease, hyperlipidemia and cerebro-vascular disease. It has antioxidant, antimicrobial, antivirus, anticancer and anti-inflammatory activities (38). Most of the allelochemical/phytotoxin work on Salvia spp. ...
... Conversely, SMR's purported effects to alleviate anaemia have not been evidenced in high-quality human trials. Yet, its ability to increase anticoagulation via inhibiting platelet aggregation is well documented [32]. SMR's active component tanshinone IIA prevents atherogenesis [33] and salvianolic acid B exhibits high vasodilator potency [34]. ...
In the fight against sports doping, the Athlete Biological Passport (ABP) system aims to indirectly unveil the doping incidents by monitoring selected biomarkers; however, several unexplored extrinsic factors may dampen a fair interpretation of ABP profiles. Chinese herbal medicine (CHM) plays a pivotal role in the health care system, and some remedies have a long history of being used to treat anaemia. In this study, we addressed the concerns of whether the CHM administration could yield a measurable effect on altering the ABP haematological variables. Forty-eight healthy volunteers were randomly assigned to receive two-week oral administration of one of the six selected CHM products that are commonly prescribed in Taiwan (eight subjects per group). Their blood variables were determined longitudinally in the phases of baseline, intervention, and recovery over 5 weeks. Blood collection and analyses were carried out in strict compliance with relevant operating guidelines. In the groups receiving Angelicae Sinensis Radix, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma, a significant increased reticulocyte percentage and decreased OFF-hr Score were manifested during the intervention, and such effects even sustained for a period of time after withdrawal. All other variables, including haemoglobin and Abnormal Blood Profile Score, did not generate statistical significance. Our results show that the use of CHM may impact the ABP haematological variables. As a consequence, we recommend athletes, particularly those who have been registered in the testing pool, should be aware of taking specific Chinese herbal-based treatment or supplementation, and document any of its usage on the anti-doping forms.
Salvia leriifolia Benth. is one of the native Iranian medicinal plants which has received attention in recent years due to its numerous therapeutic properties. The pharmaceutical properties of this species have been attributed to the presence of phenolic compounds, especially phenolic acids. The present study investigated the effect of plant age (phenology) on the gene expression and activity of phenolic acid-biosynthetic enzymes. Plant seeds were collected from Torbat-e-Heydariyeh (Khorasan Razavi province, Iran) and planted under greenhouse conditions. Leaves were sampled at 8-, 16- and 24-leaf stages of the growth period. Total contents of phenols, flavonoids, and phenolic acids were measured using spectrophotometry,
and the phenolic acid profile was determined by high-performance liquid chromatography (HPLC). The activities of phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) were measured by spectrophotometry, and the activity of rosmarinic acid synthase (RAS) was evaluated by HPLC. The relative expression of the corresponding genes was quantified by RT-PCR. The results showed that the content of all phenolic compounds and the activities of TAT and RAS enzymes/genes increased significantly (P≤0.05) with increasing plant age. At the 24-leaf stage, the total content of phenols, flavonoids, and phenolic acids were 3.47-, 2.80-, and 7.78-fold of those measured at the 8-leaf stage, respectively. The concentration of rosmarinic acid and caffeic acid (0.69 and 0.36 mg/g DW at the 8-leaf stage, respectively) increased by 3.41- and 4.05-fold during the vegetative growth, respectively. Lithospermic acid and salvianolic acids had a smaller share of total phenolic acids (0.01-0.06 mg/g DW at the 8-leaf stage), and their contents increased 2- to 10-fold with increasing plant age. Also, a strong positive correlation was observed between plant age and phenolic acid accumulation and between plant age and the activity and gene expression of TAT and RAS. TAT enzyme might
play the main role in the biosynthesis of rosmarinic acid compared to PAL.
Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.
Lithospermic acid is a phenylpropanoid oligomer isolated from an aqueous extract of dried roots of various Lamiaceae and Boraginaceae plants and used as a folk medicine to treat cardiovascular disease and to improve body functions. The manuscript has been written to provide valuable insights into naturally occurring phytocomponent, Lithospermic acid, and even explore its therapeutic potential. The data have been gathered from books and web sources, including Science Direct, Publons, Web of Science, and Scopus of the latest year. Lithospermic acid is a conjugate of rosmarinic and caffeic acid with a dihydro benzofuran nucleus and possesses a high antioxidant potential and prevents the production of superoxide radicals and lipid peroxidation and protects the tissue from deleterious effects of reactive oxygen species. In addition, it also possesses a wide range of pharmacological activities, including reducing atherosclerosis, anti-inflammatory, hepatoprotective, anti-viral, HIV-1 integrase, and hyaluronidase inhibition, aldose reductase inhibition and improvement in uremic symptoms guanidino succinic acid level. Due to its anti-HIV activity, LA has gained much attention among the scientific community. Moreover, it is widely distributed to all the peripheral tissue in rats, and its metabolites undergo enterohepatic circulation and are excreted through biliary excretion. In this review, we concluded LA with its phytochemistry, pharmacokinetics, and pharmacological activities.
Vascular wall aging has been strongly associated with cardiovascular diseases. Thus, this study aimed to investigate the efficacy of USCP-GVH-014, a mixed extract of Salvia miltiorrhiza Bunge and Paeonia lactiflora Pall., in inhibiting vascular wall aging through in vitro and in vivo experiments. The results revealed that USCP-GVH-014 inhibited abnormal cell proliferation, collagen overproduction, and MMP-2 and MMP-9 overexpression caused by various stimuli and recovered the antioxidant enzyme superoxide dismutase on human aortic smooth muscle cells. In addition, it inhibited the increase in ICAM-1 and VCAM-1 expression induced by tumor necrosis factor alpha on human aortic endothelial cells and prevented the aging of the vascular wall by regulating related proteins such as epidermal growth factor and interleukin-1 beta. Furthermore, it reduced vascular aging in in vivo studies. These results demonstrate that USCP-GVH-014 effectively reduces vascular aging, thereby rendering it a potential therapeutic candidate for cardiovascular diseases.
Salvia is one of the largest Angiosperm genera with about 1000 species. Salvia is also a well-known genus due to its medicinal importance and lever like stamens. On the basis of revisional studies and latest scientific publications, there are 115 Salvia (sage) taxa growing in Turkey, 63 taxa of which are endemic (54.7%). Molecular phylogenetic studies have revealed that the Turkish species are represented by seven clades: Zhumeria, Salvia, Sclarea, Glutinaria, Heterosphace, Dorystaechas and Rosmarinus. The distribution of species according to phytogeographical regions is as follows: 57 taxa Irano-turanian element, 31 taxa Mediterranean element, 6 taxa Euro-Siberian element and 21 taxa Multiregional element. The distribution of the threatened species according to national level is as follows: 2 taxa DD (Data Deficient), 17 taxa CR (Critically Endangered), 17 taxa EN (Endangered), 17 taxa VU (Vulnarable) and 15 taxa LC (Least Concern). The species in Turkey grow from sea level to up to ca. 3000 m, in a very wide range of different habitats. Distribution of threatened Salvia species in Turkey and the degree of their endangerement are summarized according to IUCN categories. This chapter is expected to call attention to the need to further protect the already endangered species of the important genus Salvia.
Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin–angiotensin–aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.
The entire plant Salvia cavaleriei H. Lév. (Lamiaceae) is used as a traditional Chinese herbal medicine. Its leaves are edible, and the flowers can be soaked in water to make a health-care tea. In an effort to find natural bioactive chemical components, twelve undescribed germacrane-type sesquiterpenoids, salcavalins A-L, were isolated from the whole plant of S. cavaleriei and were identified as analogs. This is the first study to isolate highly oxygenated germacrane-type sesquiterpenoids from this plant. The structures of these undescribed compounds were elucidated by various spectroscopic methods, and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation and electronic circular dichroism calculations. The biological activity of these undescribed compounds on the production of tumor necrosis factor-alpha in lipopolysaccharide induced NR8383 cells was evaluated, and salcavalins I and K showed anti-inflammatory activity to some extent. Salcavalins A-C, F and L were found to be neuroprotective with antiparkinsonic potential in a nematode (Caenorhabditis elegans) model. In addition, salcavalins F and I displayed marked phytotoxic activity against radish seeds at a low concentration of 50 ppm. Our findings provide scientific justification to show that bioactive sesquiterpenoids from the edible herb have anti-inflammatory in vitro, neuroprotective and phytotoxic activities.
Fermented wheatgrass juice was prepared using a two-stage fermentation process by employing Saccharomyces cerevisiae and recombinant Pediococcus acidilactici BD16 (alaD+). During fermentation, a reddish-brown hue appeared in wheatgrass juice due to production of different types of red pigments. The fermented wheatgrass juice has considerably higher content of anthocyanins, total phenols and beta-carotenes as compared to unfermented wheatgrass juice. It has low ethanol content, which might be ascribed to the presence of certain phytolignans in wheatgrass juice. Several yeast-mediated phenolic transformations (such as bioconversion of coumaric acid, hydroxybenzoic acid, hydroxycinnamic acid and quinic acid into respective derivatives; glycosylation and prenylation of flavonoids; glycosylation of lignans; sulphonation of phenols; synthesis of carotenoids, diarylnonanoids, flavanones, stilbenes, steroids, quinolones, di- and tri-terpenoids and tannin) were identified in fermented wheatgrass juice using an untargeted liquid chromatography (LC)-mass spectrometry (MS)-matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)/time-of-flight (TOF) technique. The recombinant P. acidilactici BD16 (alaD+) also supported flavonoid and lignin glycosylation; benzoic acid, hydroxycoumaric acid and quinic acid derivatization; and synthesis of anthraquinones, sterols and triterpenes with therapeutic benefits. The information presented in this manuscript may be utilized to elucidate the importance of Saccharomyces cerevisiae and P. acidilactici BD16 (alaD+) mediated phenolic biotransformations in developing functional food supplements such as fermented wheatgrass juice.
Phytochemical study of the Salvia santolinifolia root extract resulted in the isolation of one new quinone diterpenoid, aegyptinone E (1) as well as two known ones, aegyptinone A (2) and aegyptinone D (3). All the isolated compounds were reported for the first time from S. santolinifolia. Spectroscopic analyses including 1 D and 2 D NMR and HRESIMS were used to determine the chemical structures. Aegyptinone A (2) showed moderate antibacterial activity against Staphylococcus aureus, Staphylococcus epidermis, and Bacillus subtilis with MIC of 25 μg/mL.
Salvia miltiorrhiza and Radix Pueraria lobata herb pair is the core of the huoxuehuayu method to treat type 2 diabetes in Chinese. However, the mechanisms of this herb pair remain unclear. In this study, after fecal samples of rats were analyzed, 12 biomarkers and 15 pathways were identified by metabolomics. Then systematic pharmacology predicted 138 targets and 245 pathways. After combining these results with 3 overlapping pathways, a complete network was built. The 7 hub targets in it were verified by quantitative polymerase chain reaction (qPCR). Compared with the Model group, the mRNA level of ADCY2 (P＜0.05), MAOB, (P＜0.01), AKR1B1 (P＜0.05), XDH (P＜0.05), PDE3A (P＜0.05), and NOS2 (P＜0.01) were decreased, while the level of NOS3 (P＜0.05) was elevated after herb pair treatment. The results indicate treating effect of this herb pair is related to reducing oxidative stress, inflammation, and improving energy metabolism.
Traumatic brain injury (TBI) is a neurological disorder which represents a major health issue worldwide. It causes mortality and disability among all group ages, caused by external force, sports-related events or violence and road traffic accidents. In the USA, approximately one-third people die annually due to injury and 1.7 million people suffer from traumatic brain injury. Every year in India around 1.6 million individuals suffer from sustain brain injury with 200,000 deaths and approximately one million person needed recovery treatment at any stage of time. Sports-related head impact and trauma has become an extremely controversial public health and medico-legal problem that accounts for 20% of all brain injury (including concussion). It is difficult to reverse the primary injury but the secondary injury can be minimized by using proper pharmacological intervention during the initial hours of injury. This article highlights the pathophysiology and types of TBI along with treatment therapies. Till date, there is no single medication that can decrease the progression of the disease so that symptomatic treatment is given to the patient by determining proper pathology. Recently various herbal medicine therapies and traditional supplements have been developed for TBI. Nutritional supplementation and nutraceuticals have exposed potential in the treatment of TBI when used before and after TBI. The compiled data will enable the readers to know the pathophysiology as well as the allopathic and natural remedies to treat the TBI.
Pulmonary hypertension is a chronic and advanced disease associated with increased resistance to the pulmonary vasculature, which causes changes in the morphology of the pulmonary arteries and is a major reason for death worldwide. It is associated more in women than in men. It remains asymptomatic until the harmful effects of hypertension such as stroke, myocardial infarction, etc. are observed. Synthetic drugs are used to overcome this disease, but they produce serious side effects, so alternative medicines from medicinal plants need to be developed. Traditionally, medicinal plants have been used since ancient time and are shown to be effective. Examples of plants include Moringa Oleifera Lam, Allium sativum L., Terminalia Arjuna, Withania Somnifera, and many more. They act by decreasing SOD, increasing nitric oxide levels, and also lowering the BCL2/BAX ratio. This chapter focuses on the recent discovery of medicinal plants and its phytoconstituents used in the treatment of pulmonary hypertension and the pathways involved.
Tanshinones are the major bioactive compounds of Salvia miltiorrhiza Bunge (Danshen) roots, which are used in many therapeutic remedies in Chinese traditional medicine. We investigated the anticancer effects of tanshinones on the highly invasive human lung adenocarcinoma cell line, CL1-5. Tanshinone I significantly inhibited migration, invasion, and gelatinase activity in macrophage-conditioned medium-stimulated CL1-5 cells in vitro and also reduced the tumorigenesis and metastasis in CL1-5-bearing severe combined immunodeficient mice. Unlike tanshinone IIA, which induces cell apoptosis, tanshinone I did not have direct cytotoxicity. Real-time quantitative PCR, luciferase reporter assay, and electrophoretic mobility shift assay revealed that tanshinone I reduces the transcriptional activity of interleukin-8, the angiogenic factor involved in cancer metastasis, by attenuating the DNA-binding activity of activator protein-1 and nuclear factor-kappaB in conditioned medium-stimulated CL1-5 cells. Microarray and pathway analysis of tumor-related genes identified the differentially expressed genes responding to tanshinone I, which may be associated with the Ras-mitogen-activated protein kinase and Rac1 signaling pathways. These results suggest that tanshinone I exhibits anticancer effects both in vitro and in vivo and that these effects are mediated at least partly through the interleukin-8, Ras-mitogen-activated protein kinase, and Rac1 signaling pathways. Although tanshinone I has a remarkable anticancer action, its potential anticoagulant effect should be noted and evaluated.
Tanshinone II-A is a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza BUNGE, a traditional herbal medicine that is known to induce antiinflammatory, anti-oxidative and cytotoxic activity. We have examined cellular effects of Tanshione II-A on HL60 human promyelocytic leukemic cells and K562 human erythroleukemic cells. Tanshione II-A induced a dose- and time-dependent DNA fragmentation into the multiples of 180 bp and specific proteolytic cleavage of poly(ADP-ribose) polymerase in both cell lines. PI-staining and flow cytometry analysis of K562 cells following Tanshione II-A treatment showed an increase of the cells possessing hypodiploid DNA indicative of apoptotic state of cells. Caspase-3 activity was significantly increased during Tanshinone II-A treatment of both HL60 and K562 cells, whereas caspase-1 activity was not changed. These results suggest that Tanshione II-A induced HL60 and K562 cellular apoptosis that may be associated with the selective members of caspase family.
The purpose of this study was to investigate the possible mechanisms of Salvia miltiorrhiza (Sm) in carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. Male Wistar rats received a single dose of CCl(4) (2 ml/kg in corn oil, intraperitoneally). Three hours after CCl(4) intoxication, rats received either Sm (100 mg/kg) or silymarin (100 mg/kg) by gastrogavage twice a day for 2 consecutive days. CCl(4)-induced liver damage was shown by significant elevation of serum aminotransferase levels. Additionally, a significant decrease was observed in hepatic microsomal P450 2E1 protein content and hepatic concentrations of antioxidant enzymes. In contrast, rats given both Sm and silymarin supplement had less elevation of serum aminotransferase concentrations associated with less severe lobular damage of hepatocytes than rats receiving CCl(4) alone. Sm administration restored the reduction of hepatic microsomal P450 2E1 protein content as well as inducing an increase in hepatic glutathione concentration. On the other hand, administration of silymarin resulted in an elevation of hepatic superoxide dismutase levels. Moreover, both Sm and silymarin treatment inhibited the elevation of hepatic inducible nitric oxide (iNOS) protein content and nitrite concentration in liver homogenate 24 h after CCl(4) intoxication. We concluded that administration of Sm is effective in amelioration of CCl(4)-induced hepatotoxicity. This effect may be due to its ability to decrease the metabolic activation of CCl(4) by an increase in P450 2E1 protein content and its antioxidant activity associated with less increase in hepatic iNOS protein content.
To evaluate the effects of tanshinone II-A on inducing growth inhibition and apoptosis of human hepatocellular carcinoma (HCC) cells.
The human hepatocellular carcinoma cell line SMMC-7721 was used for the study. The cells were treated with tanshinone II-A at different doses and different times. Cell growth and proliferation were measured by MTT assay, cell count and colony-forming assay. Apoptosis induction was detected by microscopy, DNA ladder electrophoresis and flow cytometry.
In MTT assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48, 72 and 96 h after treatment with tanshinone II-A, and the most significant effect was observed at 72 h. On the other hand, the increase of doses (0.125, 0.25, 0.5, 1.0 mg/L tanshinone II-A) resulted in enhanced inhibitory effect. The growth and proliferation of SMMC-7721 cells were obviously suppressed in a dose- and time-dependent manner. The results of cell count were similar to that of MTT assay. In colony-forming assay, the colony-forming rates were obviously inhibited by tanshinone II-A. In tanshinone II-A group, the morphology of cellular growth inhibition and characteristics of apoptosis such as chromatin condensation, crescent formation, margination and apoptotic body were observed under light and transmission electron microscopes. DNA ladder of cells was presented in electrophoresis. The apoptosis index (AI) was 16.9% (the control group was 4.6%) in flow cytometry. The cells were arrested in G(0)/G(1) phase, and the expressions of apoptosis-related genes bcl-2 and c-myc were down-regulated and fas, bax, p53 up-regulated.
Tanshinone II-A could inhibit the growth and proliferation of HCC cell effectively in vitro by apoptosis induction, which was associated with up-regulation of fas, p53, bax, expression and down-regulation of bcl-2 and c-myc.
Tanshinone IIA, a major component extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, is known to exhibit potent cytotoxicity against various human carcinoma cells in vitro. However, the mechanism by which tanshinone IIA produces this anti-tumor effect remains unknown. Since anti-neovascularization has generally been regarded as an effective strategy for anti-cancer therapy, we decided to investigate the mechanism underlying tanshinone IIA-mediated death of human endothelial cells. In this study, we demonstrate that tanshinone IIA elicits human endothelial cell death independent of oxidative stress. These events are partially calcium-dependent and actually dependent upon NAD(P)H: quinone oxidoreductase (NQO1) activity. Tanshinone IIA induces an increase in intracellular calcium, which triggers the release of cytochrome c, thus causing loss of the mitochondrial membrane potential (MMP), resulting in the subsequent activation of caspases. Blocking the induction of Ca2+ perturbation with BAPTA-AM partially rescued cells from tanshinone IIA-induced cytotoxicity. Additionally, blocking NQO1 activity with dicoumoral or inhibiting caspase activities with the general caspase inhibitor, z-VAD-fmk, prevented cell death induced by tanshinone IIA. Therefore, our results imply that tanshinone IIA-mediated cytotoxicity against human endothelial cells may occur through activation of NQO1, which induces a calcium imbalance and mitochondrial dysfunction, thus stimulating caspase activity.
There is still an unresolved paradox with respect to the immunomodulating role of estrogens. On one side, we recognize inhibition of bone resorption and suppression of inflammation in several animal models of chronic inflammatory diseases. On the other hand, we realize the immunosupportive role of estrogens in trauma/sepsis and the proinflammatory effects in some chronic autoimmune diseases in humans. This review examines possible causes for this paradox.
This review delineates how the effects of estrogens are dependent on criteria such as: 1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses (e.g., T cell inhibited by estrogens vs. activation of B cell); 2) the cell types involved during different phases of the disease; 3) the target organ with its specific microenvironment; 4) timing of 17β-estradiol administration in relation to the disease course (and the reproductive status of a woman); 5) the concentration of estrogens; 6) the variability in expression of estrogen receptor α and β depending on the microenvironment and the cell type; and 7) intracellular metabolism of estrogens leading to important biologically active metabolites with quite different anti- and proinflammatory function. Also mentioned are systemic supersystems such as the hypothalamic-pituitary-adrenal axis, the sensory nervous system, and the sympathetic nervous system and how they are influenced by estrogens.
This review reinforces the concept that estrogens have antiinflammatory but also proinflammatory roles depending on above-mentioned criteria. It also explains that a uniform concept as to the action of estrogens cannot be found for all inflammatory diseases due to the enormous variable responses of immune and repair systems.
OBJECTIVE: TO discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhiza Bge, and warfarin. DATA SOURCES: A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. Ail articles written in English or with an English extract were considered for review. STUDY SELECTION AND DATA EXTRACTION: Ail studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed. DATA SYNTHESIS: Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III-like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen. CONCLUSIONS: Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.
The essential oil from the air-dried leaves of Salvia miltiorrhiza Bunge, collected from Qinling Mountains of China during the blooming stage, was obtained by hydrodistillation and analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). Hexadecanoic acid (17.0%), germacrene D (9.1%), phytol (8.9%), β-caryophyllene (7.1%) and methyl linolenate (5.3%) were the main components (73.3%). The oil showed moderate antibacterial activity against Bacillus coagulans, Staphylococcus albus and Staphylococcus aureus. The oil sample also showed some antioxidant activities in the 2,2-diphenylpicrylhydrazyl (DPPH.) and β-carotene/linoleic acid assays.
OBJECTIVES
We tested the hypothesis that the reperfusion syndrome (RS), defined as an additional elevation of the ST segment upon reperfusion, may be a marker of microcirculatory reperfusion injury during acute myocardial infarction (AMI).BACKGROUND
The pathophysiology of the RS is unknown, and its prognostic implications are controversial.METHODS
Twenty-one patients with an anterior AMI treated ≤12 h after onset by primary coronary angioplasty (PTCA) were studied. Coronary velocity reserve (CVR), an index of microcirculatory function, was measured using a Doppler guidewire. Left ventricular (LV) ejection fraction, infarct size (percent defect) and LV end-systolic volume index (LVESVi) were evaluated by radionuclide ventriculography, 201T1 single-photon emission computed tomography and contrast ventriculography, respectively.RESULTSBaseline ST elevation and pain-to-TIMI 3 time were similar in patients with and without RS. Patients with RS (10/21) had a lower post-PTCA CVR than patients without RS (median [95% confidence interval]: 1.2 [1–1.3] vs. 1.6 [1.5–1.7], p < 0.005). Even though predischarge CVR was similar in the two groups, infarct size at six weeks (26 [21 to 37] vs. 14 [10–17] % 201T1 defect, p = 0.001) and predischarge LVESVi (45% [40 to 52] vs. 30% [29 to 38] mL/m2, p = 0.001) were larger, and LV ejection fraction at six weeks (40% [37 to 46] vs. 55% [50 to 60], p = 0.004) was lower in patients with RS than in patients without RS.CONCLUSIONS
Patients with RS during primary PTCA for an anterior AMI have a transiently lower CVR than patients without RS, but sustained LV dysfunction and larger infarct size, suggesting that RS is a marker of microcirculatory reperfusion injury.
Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body. Free-radical mechanisms have
been implicated in the pathology of several human diseases, including cancer, atherosclerosis, malaria, and rheumatoid arthritis
and neurodegenerative diseases. For example, the superoxide radical (O
2
·−
) and hydrogen peroxide (H2O2) are known to be generated in the brain and nervous system in vivo, and several areas of the human brain are rich in iron, which appears to be easily mobilizable in a form that can stimulate
free-radical reactions. Antioxidant defenses to remove O
2
·−
and H2O2 exist. Superoxide dismutases (SOD) remove O
2
·−
by greatly accelerating its conversion to H2O2. Catalases in peroxisomes convert H2O2 into water and O2 and help to dispose of H2O2 generated by the action of the oxidase enzymes that are located in these organelles. Other important H2O2-removing enzymes in human cells are the glutathione peroxidases. When produced in excess, ROS can cause tissue injury. However,
tissue injury can itself cause ROS generation (e.g., by causing activation of phagocytes or releasing transition metal ions
from damaged cells), which may (or may not, depending on the situation) contribute to a worsening of the injury. Assessment
of oxidative damage to biomolecules by means of emerging technologies based on products of oxidative damage to DNA (e.g.,
8-hydroxydeoxyguanosine), lipids (e.g., isoprostanes), and proteins (altered amino acids) would not only advance our understanding
of the underlying mechanisms but also facilitate supplementation and intervention studies designed and conducted to test antioxidant
efficacy in human health and disease.
Antioxidative activity and total phenolic compounds of root, leaf and petiole of four accessions of Centella asiatica (L.) Urban, namely CA 01, CA 05, CA 08 and CA 11, were evaluated. Antioxidative activity of the extracts was measured using the ferric thiocyanate (FTC) method and thiobarbituric acid (TBA) test. The antioxidative activities were then compared with that of α-tocopherol (natural antioxidant) and butylated hydroxytoulene or BHT (synthetic antioxidant). The results showed that CA 01 and CA 05 had the highest antioxidative activities among the accessions tested. Results also showed that both leaf and root of C. asiatica had high antioxidative activity, which was as good as that of α-tocopherol. The total phenolic content, determined according to the Folin–Ciocalteu method, varied from 3.23 to 11.7 g/100 g dry sample, and showed strong association (r2=0.90) with antioxidative activity. The results suggest that phenolic compounds are the major contributors to the antioxidative activities of C. asiatica.
Antioxidant activity of ethyl acetate extracts from rice koji (EAERK) fermented with Aspergillus candidus CCRC 31543 was evaluated, and the antioxidant components in koji were isolated and identified. EAERK (200 μg/ml) showed a 90% inhibitory effect on peroxidation of linoleic as determined by the thiocyanate method. EAERK also showed a marked antioxidant activity on the oxidation of lard determined by using the Rancimat method. EAERK had a strong scavenging effect on the DPPH radical. Silica gel column chromatography was used to separate EAERK into eight fractions (A–H). Fractions C–F possessed significant antioxidant activity and showed more than 88% inhibition of peroxidation of linoleic acid. Fraction C was crystallized and purified to obtain compound 1. Fractions D–F were combined and re-separated by means of column chromatography and the subfraction that exhibited strong antioxidant activity was crystallized to yield purified compound 2. Compounds 1 and 2 were shown to be ergosterol and terphenyllin, respectively, on the basis of UV-vis spectral, MS and NMR analyses. Ergosterol showed no antioxidant activity on the peroxidation of linoleic acid. However, the antioxidant activity of terphenyllin was equal to that of BHA at 200 μg/ml.
Pharmacological control of interleukin-12 (IL-12) and interferon-gamma (IFN-γ) production may be a key therapeutic strategy for modulating immunological diseases dominated by Th1-derived cytokine responses. In this study, we investigated the effects of three different tanshinone pigments from Salvia miltiorrhiza (tanshinone I, dihydrotanshinone, and cryptotanshinone) on IL-12 production in mouse macrophages and on IFN-γ production in lymph node cells. All tested tanshinones significantly inhibited IL-12 production in lipopolysaccharide (LPS)-activated macrophages and also IFN-γ production in keyhole limpet hemocyanin (KLH)-primed lymph node cells in a dose-dependent manner. Dihydrotanshinone was more effective than tanshinone I or cryptotanshinone. Tanshinones significantly inhibited the expression of IL-12 p40 gene at the mRNA level. Furthermore, tanshinones potently inhibited the promoter activation of IL-12 p40 gene and nuclear factor (NF)-κB binding to the κB site, suggesting that tanshinones may negatively regulate IL-12 production at the transcription level. These results may explain some known biological activities of tanshinones including their anti-inflammatory effect, and suggest a possible use of tanshinones in the treatment of immunological diseases dominated by Th1-derived cytokine responses.
This review summarizes the recent advances in the chemical analysis of Danshen and its finished products, including the introduction of the identified bioactive components, analytical methods for quantitative determination of target analytes and fingerprinting authentication, quality criteria of Danshen crude herb and its preparations, as well as the pharmacokinetic and pharmacodynamic studies on the active components of Danshen and its finished products. Danshen contains mainly two types of constituents, the hydrophilic depsides and lipophilic diterpenoidal quinones and both of them are responsible for the pharmacological activities of Danshen. In order to monitor simultaneously both types of components which have different physicochemical properties, numerous analytical methods have been reported using various chromatographic and spectrophotometric technologies. In this review, 110 papers on analysis of Danshen are discussed, various analytical methods and their chromatographic conditions are briefly described and their advantages/disadvantages are compared. For obtaining a quick, accurate and applicable analytical approach for quality evaluation and establishing a harmonized criteria of Danshen and its finished products, the authors’ suggestion and opinions are given, including the reasonable selection of marker compounds with high concentration and commercial availability, a simple sample preparation procedure with high recoveries of both the hydrophilic phenols and lipophilic tanshinones, and an optimized chromatographic condition with ideal resolutions of all the target components. The chemical degradation and transformation of the predominant constituent salvianolic acid B in Danshen during processing and manufacturing are also emphasized in order to assure the quality consistency of Danshen containing products.
Salvia miltiorrhiza is a Chinese herb widely used for cardiovascular disorder regimens, yet little is known about the cellular mechanisms that contribute to attenuated growth of smooth muscle cells (SMCs) under oxidative stress such as homocysteine (Hcy) treatment. As anticipated, a low dose (0.015 mg/mL) of S.miltiorrhiza aqueous extract (SMAE) significantly inhibited (>60%) the growth of a rat smooth muscle cell line (A10) under Hcy stimulation and the intracellular reactive oxygen species (ROS) concentration obviously decreased after SMAE treatment in terms of reducing p47(phox) translocation and increasing catalase activity. Signaling profile suggests that SMAE inhibited Hcy-induced A10 cell growth via the PKC/MAPK-dependent pathway. Two-dimensional electrophoresis (2-DE) coupled with mass spectrometry revealed statistically significant changes in the intensity of 14 proteins in response to Hcy and Hcy/SMAE. Meanwhile, SMAE attenuated carbonyl-modification of specific cytoskeleton and chaperone proteins leading to cell type transformation. Moreover, a network analysis using MetaCore shed more light on the molecular basis associated with SMAE efficacy. SMAE exerts its protective effect through the scavenging of ROS and subsequent modulation of protein carbonylation to inhibit cell proliferation. These signature networks and functional proteomics highlighted herein may facilitate the evaluation of potential therapeutic targets and elucidate novel mechanisms through which protein functions can be regulated by the redox status.
It is reported that salvianolic acid B, a bioactive phenolic compound contained in the root of Salvia miltiorrhiza, exhibits a much stronger activity in free radical scavenging and antioxidance than those of vitamin E. When a conventional refluxing method is adopted to extract salvianolic acid B from the root, in which the materials are subjected to higher temperature and longer time, the yield of this phenolic compound is lower due to the possibility of its hydrolysis to tanshinol. However, a higher extraction yield can be achieved over a shorter time period and lower temperature when an ultrasound-assisted extraction method is used. This paper investigated the parameters influencing the extraction of salvianolic acid B. Factors such as extraction time, frequency of the ultrasound, the ratio of solvent to material, and types of extraction solvent were examined. A comparison was also conducted between conventional refluxing and ultrasound-assisted extraction. Results showed that the optimal parameters to extract salvianolic acid B from the root of S. miltiorrhiza were as follows: ultrasonic frequency: 45 Hz; solvent: 60% aqueous ethanol; extraction temperature: 30 degrees C; extraction time duration: 25 min.; ratio of solvent to material: 20:1 (v/w, ml/g). Under these conditions, the yield of salvianolic acid B was 5.17 mg/g (33.93 mg/g) higher than those with conventional refluxing method (28.76 mg/g), indicating that the efficiency and the yield of ultrasound-assisted extraction method are higher than reflux method, and the hydrolysis of salvianolic acid B to tanshinol is effectively avoided.
Water-soluble salvianolic acid A (Sal A) and salvianolic acid B (Sal B) were successfully isolated and purified from the crude extract of Salvia miltiorrhiza by high-speed counter-current chromatography (HSCCC). The solvent system was n-hexane-ethyl acetate-methanol-water (3:6:6:10, v/v/v/v). 4.27 mg of Sal A and 32.09 mg of Sal B were obtained from 260 mg of the crude sample. The purities of Sal A and Sal B were 96.67% and 97.43%, respectively. Their structures were identified by (1)H NMR and (13)C NMR. Antioxidant activities of Sal A and Sal B were also evaluated and compared by the methods of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS(+)) radical cation decolourisation assay. Both Sal A and Sal B showed high radical scavenging activities with their EC(50) values being 1.43+/-0.09 and 1.81+/-0.01 microg/ml in DPPH radical method. The ABTS results showed that Sal A and Sal B exhibited high total antioxidant activities, their EC(50) values were 1.35+/-0.00 and 1.43+/-0.01 microg/ml, respectively.
Tanshinone I (Tan-I) and tanshinone IIA (Tan-IIA) were isolated from Danshen (Salviae Miltiorrhizae Radix), a widely prescribed traditional herbal medicine that is used to treat cardiovascular and dysmenorrhea diseases. In our previous study, Tan-IIA was demonstrated to induce apoptosis in human colon cancer Colo 205 cells. However, the effect of Tan-I on human colon cancer cells is not clearly understood yet. In this study, the anti-growth and apoptosis-eliciting effects of Tan-I, as well as its cellular mechanisms of actions, were investigated in Colo 205 human colon cancer cells. Tan-I reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and in cells in the sub-G1 fraction. The expression of p53, p21, bax and caspase-3 increased in Tan-I-treated cells. In addition, the cell cycle analysis showed G0/G1 arrest. These findings suggest that Tan-I induces apoptosis in Colo 205 cells through both mitochondrial-mediated intrinsic cell-death pathways and p21-mediated G0/G1cell cycle arrest. Accordingly, the therapeutic potential of Tan-I for colon cancer deserves further study.
The study aimed at evaluating the hypolipidemic effects of Purified Salvia miltiorrhiza extract (PSME) and investigating the potential molecular mechanisms by which PSME modulated lipid profiles in hyperlipidemic rats.
Sprague-Dawley male rats on a high-fat/high-cholesterol diet were treated orally with PSME, GW3965 (a selective liver X receptor agonist) or vehicle alone. Gene expression analysis and transactivation assays were used to clarify the molecular mechanisms of action of PSME.
The concentrations of plasma total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol) and triglycerides in rats treated with PSME at 150 mg kg day(-1) were significantly decreased (P < 0.01), accompanied with significantly decreased concentrations of liver total cholesterol and triglycerides (P < 0.01). In both drug-treated rats, the concentration of high-density lipoprotein cholesterol (HDL-cholesterol) was significantly elevated (P < 0.01). Intriguingly, short heterodimer partner (SHP) mRNA level was significantly higher in PSME-treated rats (P < 0.01), accompanied with the significantly decreased mRNA level of sterol regulatory element binding protein 1c (SREBP1c) (P < 0.01), which contributed to the decreases of liver and plasma triglycerides through a farnesoid X receptor-SHP-SREBP1c pathway. ATP-binding Cassette Transporter B11 (ABCB11) and murine Mdr2 P-glycoprotein (also known as ABCB4) were significantly induced by PSME, which were responsible for biliary cholesterol solubility by proper biliary secretion of bile salts and phospholipids. The transactivation assays were used to identify PSME as a farnesoid X receptor/liver X receptor alpha coagonist.
These results indicated that PSME as a farnesoid X receptor/liver X receptor alpha coagonist largely improved the lipid profiles in the hyperlipidemic rats.
Fifteen tanshinone analogues isolated from the chloroform extract of Danshen roots (Salviae Miltiorrhizae Radix) by chromatographic procedures were tested for their cytotoxic activities against KB, Hela, Colo-205 and Hep-2 carcinoma cell lines. Several of them were effective at concentrations below 1 micrograms/ml concentrations. Tanshinone analogues with either hydroxy substitutions or olefinic feature in ring A demonstrated higher biologic activities. Analysis of structure-activity relationship indicate that the basic requirement for activity is the presence of a furano-o-naphthoquinone in the molecule. Compounds which lack an intact furan ring were found to be inactive. It is suggested that the planar phenanthrene ring of the tanshinones may be essential for interaction with DNA molecule whereas the furano-o-quinone moiety could be responsible for the production of reactive free radicals in the close vicinity of the bases to cause DNA damage.
Two new diterpenoids, designated neocryptotanshinone and isotanshinone IIB, have been isolated from "Tan-Shen," the root of Salvia miltiorrhiza, together with a known compound, danshexinkun A. Their structures are established by spectral and physical data. Isotanshinone IIB exhibits significant inhibitory activity in vitro on ADP- and collagen-induced aggregation.
Carcinogenicity tests showed that addition of the antioxidant BHA to the diet of F344 rats induced high incidences of papilloma and squamous cell carcinoma of the forestomach of both sexes. Male hamsters given BHA for 24 weeks also developed papilloma showing downward growth into the submucosa of the forestomach. These results indicate that BHA should be classified in the category of "sufficient evidence of carcinogenicity" as judged by IARC criteria. The 3-tert isomer of BHA seemed to be responsible for the carcinogenicity of crude BHA in the forestomach of rats. BHT was not found to be carcinogenic in rats or mice. In two-stage carcinogenesis in rats after appropriate initiation, BHA enhanced carcinogenesis in the forestomach and urinary bladder of rats, but inhibited carcinogenesis in the liver. BHT enhanced the induction of urinary bladder tumors and inhibited that of liver tumors, but had no effect on carcinogenesis in the forestomach. BHT could be a promoter of thyroid carcinogenesis. Sodium L-ascorbate enhanced forestomach and urinary bladder carcinogenesis. Ethoxyquin enhanced kidney and urinary bladder carcinogenesis, but inhibited liver carcinogenesis. Thus, these antioxidants modify two-stage chemical carcinogenesis in the forestomach, liver, kidney, urinary bladder, and thyroid, but show organ-specific differences in effects.
Sodium tanshinone IIA sulfonate (STS) is a derivative of tanshinone IIA. The latter is a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza. Liquid chromatographically pure STS was found to reduce myocardial infarct size by 53.14 +/- 22.79% relative to that in the saline control in a rabbit 1 hr-ischemia and 3 hr-reperfusion model. This effect was comparable to that of Trolox (a better characterized antioxidant serving as a reference cytoprotector), which salvaged the myocardium in the same infarct model by 62.13 +/- 18.91%. Also, like Trolox, STS did not inhibit oxygen uptake by xanthine oxidase (XO), a key enzyme in free radical generation. However, in contrast to Trolox, STS significantly prolonged the survival of cultured human saphenous vein endothelial cells but not human ventricular myocytes in vitro when these cells were separately exposed to XO-generated oxyradicals. Note that the endothelium is recognized to be a key site of oxidant generation and attack. Our findings in vitro and in vivo support the interpretation that STS is a cardioprotective substance, and that it may exert a beneficial effect on the clinically important vascular endothelium.
Yu CM, Chan JCN, Sanderson JE (Department of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong). Chinese herbs and warfarin potentiation by 'Danshen'. J Int Med 1997: 241: 337-9. Drug interactions with warfarin can be dangerous and although common drug interactions are now well recognized those with Chinese herbs are not widely appreciated. 'Danshen' is a herbal medicine often used for various complaints, particularly cardiovascular, in the Chinese community. We report a case of danshen-induced overcoagulation with severe and dangerous abnormalities of clotting in a patient with rheumatic heart disease.
The cytotoxicity-guided fractionation of the roots of Salvia miltiorrhiza B. (Labiatae) extracts led to the isolation of eighteen active principles 1-18, responsible for the cytotoxicity against five cultured human tumor cell lines, i.e., A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon), using the SRB (sulfrhodamine-B) method in vitro. All active compounds 1-18 including two novel components 5 and 11 were comprised of tanshinone pigments, unusual diterpenes exclusively found in this species. The proliferation of each examined tumor cell line was significantly inhibited (IC50 values ranged from 0.2 to 8.1 micrograms/ml) during the continuous exposure of tumor cells to 1-18 for 48 hours, respectively.
We report a case of profound anticoagulation caused by interaction between warfarin and danshen, a widely used Chinese herbal medicine, in a patient who had undergone mitral valve replacement. Patients taking warfarin should be warned not to take this herb. In addition, physicians should be alert to the possibility of an interaction with herbal medicine when anticoagulation control becomes difficult and no other causes are apparent. (Ann Thorac Surg 1998;66:941-2) (C) 1998 by The Society of Thoracic Surgeons.
Cryptotanshinone and dihydrotanshinone I, constituents of a medicinal plant, Salvia miltiorrhiza Bunge, had antibacterial activity against a broad range of Gram positive bacteria. These compounds generated superoxide radicals in Bacillus subtilis lysates. A recombination-deficient mutant strain of B. subtilis was 2- to 8-fold more sensitive than a wild strain, and this hypersensitivity was reduced in the presence of dithiothreitol as an antioxidant. DNA, RNA, and protein syntheses in B. subtilis were non-selectively inhibited by these compounds. These results suggest that superoxide radicals are important in the antibacterial actions of the agents.
To discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhiza Bge, and warfarin.
A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. All articles written in English or with an English extract were considered for review.
All studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed.
Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III-like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen.
Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.
The activation of stress-activated protein (SAP) kinase may lead to an induction of apoptosis that is responsible for part of the cardiomyocyte death in reperfusion injury. The objective of the present study was to investigate the mechanism by which magnesium tanshinoate B (MTB), a bioactive compound isolated from Danshen, prevents apoptosis in cardiomyocytes in the ischemic/reperfused heart. Isolated adult rat hearts were perfused by the Langendorff mode with medium containing MTB prior to the induction of normothermic global ischemia. At the end of the 30-min ischemic period, the heart was reperfused with the same medium with or without MTB for an additional 20 min. In the MTB-treated ischemic/reperfused heart, the number of apoptotic nuclei was reduced by 2.5-fold in comparison to that in untreated ischemic/reperfused controls [23 +/- 4 vs 57 +/- 7 (mean +/- SD) TUNEL-positive cells, respectively, N = 3-4, P < 0.001]. SAP kinase activity was elevated 1.7-fold in ischemic/reperfused rat hearts [35.6 +/- 3.8 vs 21.2 +/- 3.3 (control) (mean +/- SEM) relative densitometric units, N = 4-6, P < 0.05]. Treatment with MTB abolished this elevation in SAP kinase activity (25.0 +/- 5.2 relative densitometric units), which was also decreased by 40% in the nucleus. When the heart was subjected to ischemia alone, there was no significant change in SAP kinase activity in the presence or absence of MTB. MTB did not appear to affect the p38 mitogen-activated protein kinase activity in this model system. In conclusion, MTB was shown to have cardioprotective activity against apoptosis, probably through the inhibition of SAP kinase activity.
Antioxidants that prevent low density lipoproteins (LDL) from oxidation may inhibit atherosclerosis and post-angioplasty restenosis. Salvia miltiorrhiza (SM) has been shown to inhibit LDL oxidation and reduce atherosclerosis in cholesterol-fed rabbits. The effects of SM on neointimal hyperplasia and monocyte chemotactic protein-1 (MCP-1) expression after balloon injury were studied. Male New Zealand white rabbits were fed a 2% cholesterol diet together with daily SM (4.8 gm/kg body wt.) treatment (SM; n=10) or without SM as a control (C; n=9) for 6 weeks. Probucol-treated (0.6 gm/kg body wt.) rabbits (P; n=9) were used as a positive control group. A balloon injury of the abdominal aorta was performed at the end of the third week. Aortas were harvested at the end of 6 weeks. The plasma cholesterol levels were lowered in SM group. The neointimal hyperplasia in abdominal aortas was significantly inhibited in SM group [neointima/media area ratio: 0.63+/-0.05 (SM) versus 0.78+/-0.05 (C); P < 0.05] and in P group [0.45+/-0.02 (P) versus 0.78+/-0.05 (C); P < 0.05] when compared with C group. SM treatment significantly reduced MCP-1 mRNA and protein expression in balloon-injured abdominal aorta. These inhibitory effects on intimal response after balloon injury might be attributed to antioxidant capacity and cholesterol lowering effect of SM. SM treatment may offer some protection against post-angioplasty restenosis.
Recent studies have demonstrated that induction of apoptosis is related to the cell growth inhibition potential of Salvia Miltiorrhiza (SM), a traditional herbal medicine. In the present study, we further explore the mechanistic pathway involved in SM-induced apoptosis in human hepatoma HepG2 cells. A rapid decline of intracellular glutathione (GSH) and protein thiol content was found in SM-treated cells. Moreover. SM exposure resulted in mitochondrial dysfunction as demonstrated by: (i) the onset of mitochondrial permeability transition (MPT); (ii) the disruption of mitochondrial membrane potential (MMP); and (iii) the release of cytochrome c from mitochondria into the cytosol. Subsequently, elevated level of intracellular reactive oxygen species (ROS) was observed prior to the onset of DNA fragmentation. However, no caspase-3 cleavage was observed throughout the whole period of SM treatment, while a caspase-3-independent poly(ADP-ribose) polymerase (PARP) cleavage was noted at the late stage in SM-induced apoptosis. Pretreatment of cells with N-acetylcysteine (NAC), the GSH synthesis precursor, conferred complete protection against MMP loss, ROS generation and apoptosis induced by SM. MPT inhibitors, cyclosporin A plus trifluoperazine, partially restored intracellular GSH content, and reduced SM-induced ROS formation and subsequently inhibited cell death. Moreover, antioxidants NAC, deferoxamine and catalase had little effect on GSH depletion and mitochondrial dysfunction, yet still were able to completely protect cells from SM-induced apoptosis. Taken together, our results suggest that SM deplete intracellular thiols, which, in turn, causes MPT and subsequent increase in ROS generation, and eventually apoptotic cell death.
AIM:To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer cells.METHODS:Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation wasdetected.RESULTS:The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid.Flow cytometric assay demonstrated that S phase cells decreased and G(0)/G(1) phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly increased. CONCLUSION:Tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.
Water soluble extracts of the herbal plant, Salvia miltiorrhiza (Danshen) exhibited potent effect against HIV-1 integrase activity in vitro and viral replication in vivo. We have developed an extensive purification scheme to isolate effective, non-toxic inhibitors against human immunodeficiency virus type 1 (HIV-1) using the 3'-processing activity of integrase as a purification guide and assay. Two water soluble compounds, M(5)22 and M(5)32, have been discovered by isolating them from S. miltiorrhiza roots in purities of >99.5% as shown by NMR spectral analysis with yields of 0.018 and 0.038%, respectively. Structural determination revealed that M(5)22 is lithospermic acid and M(5)32 is lithospermic acid B. These two structurally related compounds are potent anti-HIV inhibitors and showed no cytotoxicity to H9 cells at high concentrations (CC(100)>297 microM for M(5)22 and >223 microM for M(5)32). The IC50 for inhibition of 3'-processing by HIV-1 integrase was found to be 0.83 microM for M(5)22 and 0.48 microM for M(5)32. In addition, M(5)22 and M(5)32 inhibited HIV-1 integrase catalytic activities of 3'-joining to the target DNA with IC50 of 0.48 microM for M(5)22 and 0.37 microM for M(5)32. Furthermore, kinetic and mechanistic studies suggested that drug binding to HIV-1 integrase and inhibition of enzymatic activity occur at a fast rate. Both M(5)22 and M(5)32 do not prevent HIV entry in H9 cells. They also show no inhibition of reverse transcriptase activity in infected cells. The levels of intracellular strong stop and full-length viral DNA remained unchanged following drug treatment. However, both inhibitors strongly suppressed the acute HIV-1 infection of H9 cells with IC50 values of 2 and 6.9 microM for M(5)22 and M(5)32, respectively. Thus these two selective integrase inhibitors hold promise as a novel class of therapeutic drugs for AIDS based on their high potencies and absence of cytotoxicity.
Arachidonic acid (AA) mainly released from the cell membrane by phospholipase A(2) (PLA(2)) is converted to eicosanoids by the action of cyclooxygenase (COX) and lipoxygenase (LO). In order to find the specific inhibitors of AA metabolism especially PLA(2) and COX-2, 300 plant extracts were evaluated for their inhibitory activity on PGD(2) production from cytokine-induced mouse bone marrow-derived mast cells in vitro. From this screening procedure, the methanol extract of Salvia miltiorrhiza was found to inhibit PGD(2) production and the ethyl acetate subfraction gave the strongest inhibition of five subfractions tested. From this ethyl acetate subfraction, an activity-guided isolation finally gave tanshinone I as an active principle. This investigation deals with the effects of tanshinone I on AA metabolism from lipopolysaccharide (LPS)-induced RAW 264.7 cells and in vivo antiinflammatory activity. Tanshinone I inhibited PGE(2) formation from LPS-induced RAW macrophages (IC(50) = 38 microM). However, this compound did not affect COX-2 activity or COX-2 expression. Tanshinone I was found to be an inhibitor of type IIA human recombinant sPLA(2)(IC(50) = 11 microM) and rabbit recombinant cPLA(2) (IC(50) = 82 microM). In addition, tanshinone I showed in vivo antiinflammatory activity in rat carrageenan-induced paw oedema and adjuvant-induced arthritis.
Cinnamoyl, p-coumaroyl, feruloyl, caffeoyl aloesin, and related compounds were isolated from Aloe species. The antiinflammatory and antioxidative activities of these compounds were examined based on the structure-activity relationship. It was suggested that the bioactivities may link to acyl ester groups in aloesin, together with those of aloesin-related compounds. However, investigations using the contact hypersensitivity response indicated a preventive effect of aloesin on the UV-B-induced immune suppression. Furthermore, aloesin inhibited tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates. These results show that aloesin prevents not only UV-B-induced immune suppression, but also could be a positive pigment-altering agent for cosmetic application. In preclinical study, aloe extract was investigated using phagocytosis and nitroblue tetrazolium chloride (NBT) reduction in adult bronchial asthma, and high molecular-weight materials, such as polysaccharide and glycoprotein fractions, were identified as active ingredients. The neutral polysaccharides, aloemannan and acemannan showed antitumor, antiinflammatory and immunosuppressive activities, and glycoprotein fractions with bradykinindegrading and cell proliferation-stimulating activities were identified from the nondialysate fraction of the gel part of Aloe species. Verectin fractionated from Aloe vera gel was examined biochemically and immunochemically, and verectin antibody was used in the appraisal of commercial Aloe vera gel products. It was reported that aloesin stimulates the proliferation of cultured human hepatoma SK-Hep 1 cells. Thus aloesin, related compounds, and high molecular-weight materials, such as aloemannan and verectin, may act in concert to exert therapeutic properties for wounds, burns and inflammation. The biodisposition of fluoresceinylisothiocyanate (FITC)--labeled aloemannan (FITC-AM) with the homogenate from some organs in mice was demonstrated, and FITC-AM was metabolized to a smaller molecule (MW 3000) by the large intestinal microflora in feces. The modified aloe polysaccharide (MW: 80000) with cellulase under restricted conditions, immunologically stimulated the recovery of UV-B-induced tissue in jury. Thus the modified polysaccharides of aloemannan, together with acemannan (MW: about 600000), are expected to participate in biological activity following oral administration. The effects of tanshinone VI, a diterpenoid isolated from Salvia miltiorrhiza, on the heart are reviewed. First, the effects on the posthypoxic recovery of contractile function of perfused rat hearts were examined. Hypoxia/reoxygenation induced a release of purine nucleosides and bases (ATP metabolites) and resulted in little recovery of contractile force of reoxygenated hearts. Pretreatment of the perfused heart with 42 nM tanshinone VI under hypoxic conditions attenuated the release of ATP metabolites during hypoxia/reoxygenation. Treatment with tanshinone VI enhanced the posthypoxic recovery of myocardial contractility. These results show that tanshinone VI may protect the heart against hypoxia/reoxygenation injury and improve the posthypoxic cardiac function. Second, the effects of tanshinone VI on in vitro myocardial remodeling were examined. Cardiomyocytes and cardiac fibroblasts were isolated from neonatal rat hearts, and simultaneously prepared insulin-like growth factor-1 (IGF-1) induced the hypertrophy of cardiomyocytes. IGF-1 increased the collagen synthesis of cardiac fibroblasts, that is, in vitro fibrosis. The hypertrophy of cardiomyocytes was attenuated in the presence of tanshinone VI in the culture medium. The fibrosis of cardiac fibroblasts was decreased by treatment with tanshinone VI. When tanshinone VI was added to cardiac fibroblast-conditioned medium, the medium-mediated hypertrophy of cardiomyocytes was also attenuated. These results show that tanshinone VI may attenuate in vitro cardiac remodeling. The series of studies has shown that tanshinone VI protects the myocardium against hypoxia/reoxygenation injury and attenuates progression of in vitro myocardial remodeling, suggesting that tanshinone VI is a possible agent for the treatment of cardiac disease with contractile failure.
Apoptosis, or programmed cell death, has an essential role in controlling cell number in many developmental and physiological settings and in chemotherapy-induced tumour-cell killing. It is a genetically regulated biological process, guided by the ratio of proapoptotic and antiapoptotic proteins. Recently, inducers of apoptosis have been used in cancer therapy. Several studies have attempted to induce apoptosis by triggering the tumour-necrosis-factor-related apoptosis-inducing ligand receptor and the BCL2 family of proteins, and others have targeted the caspases, and proteins that inhibit apoptosis. Most of these therapies are still in preclinical development because of their low efficacy and susceptibility to drug resistance, but some of them have shown promising results. In this article, we review the development and clinical efficacy of proapoptotic drugs that have shown promise.
Neo-tanshinlactone (1) was isolated and synthesized for the first time and evaluated in vitro against several human cancer cell lines. Compound 1 showed significant inhibition against two ER+ human breast cancer cell lines and was 10-fold more potent and 20-fold more selective as compared to tamoxifen citrate. Compound 1 also potently inhibited an ER-, HER-2 overexpressing breast cancer cell line. Therefore, this novel compound merits further development as an anti-breast cancer drug candidate.
Danshen, the dried root of Salvia miltiorrhiza, has been widely used in China and, to a lesser extent, in Japan, the United States, and other European countries for the treatment of cardiovascular and cerebrovascular diseases. In China, the specific clinical use is angina pectoris, hyperlipidemia, and acute ischemic stroke. The current review covers its traditional uses, chemical constituents, pharmacological activities, pharmacokinetics, clinical applications, and potential herb-drug interactions based on information obtained in both the English and Chinese literature. Although numerous clinical trials have demonstrated that certain Danshen products in China are effective and safe for the treatment of cardiovascular diseases, most of these lack sufficient quality. Therefore, large randomized clinical trials and further scientific research to determine its mechanism of actions will be necessary to ensure the safety, effectiveness, and better understanding of its action.
Lipopolysaccharide (LPS) has been implicated as one of the major cause of Gram-negative bacteria-induced sepsis that are life-threatening syndromes occurring in intensive care unit patients. Many natural products derived from medicinal plants may contain therapeutic values on protecting endotoxemia-induced sepsis by virtue their ability to modulate multiple pro-inflammatory cytokines. In the present study, we show that Salvia miltiorrhiza (SM) BUNGE or Danshen, used in treatment of various systemic and surgical infections in the hospitals of China, was able to block the lethal toxicity of LPS in mice via suppression of TNF-alpha release and protection on liver injury. The ability of SM to suppress LPS-induced TNF-alpha release is further confirmed by in vitro experiments conducted on human peripheral blood leukocytes (PBL) and the RAW 264.7 macrophage cell line. Immunophenotyping by flow cytometry shows improved T-helper cell (CD4) and T-suppressor cells (CD8) ratio in SM-treated PBL and splenocytes of LPS-challenged mice. The drop in plasma glutamate-pyruvate transaminase (GPT) induced by LPS provides evidence that SM can protect hepatic damage. The present study explains some known biological activities of SM, and supports the clinical application of SM in the prevention of inflammatory diseases induced by Gram-negative bacteria.
To study the in vitro antimicrobial activity of ethanol extract of salvia miltiorrhiza bunge on several oral pathogenic microbes.
Antimicrobial activities of ethanol extract of salvia miltiorrhiza bunge for porphyromonas gingivalis ATCC 33277, A. actinomycetes comitans ATCC 24523, Streptococcus mutans, and Lactobacillus were determined using the cup-plate method. The minimum antibacterial concentrations of ethanol extract of salvia miltiorrhiza bunge were measured. SPSS10.0 software package was used for Student's t test.
Ethanol extract of salvia miltiorrhiza bunge had antimicrobial activities on Porphyromonas gingivalis, A. actinomycetemcomitans, Streptococcus mutans, Lactobacillus, and the minimum inhibitory concentrations were 15.62 mg/ml, 15.62 mg/ml, 62.50mg/ml and 15.62 mg/ml; The pH of the solution was influential to its antimicrobial activity.
Ethanol extract of salvia miltiorrhiza bunge has an antimicrobial activity on oral pathogenic microbes.
The present study was undertaken to evaluate plasma TNFalpha, IL-1beta, IL-10; and urinary hydroxyproline (Hyp) and calcium (Ca) as bone resorption markers in postmenopausal women compared with premenopausal ones; and to assess the effects of HRT upon these cytokines and bone turnover markers.
The study involved 50 healthy postmenopausal women, and 25 healthy premenopausal women (control group). Postmenopausal women were randomly divided into two subgroups: women receiving cycle HRT schedule (0.625 mg conjugated estrogen from days 1 to 28+5 mg medroxyprogesterone acetate from days 18 to 28) for 2 months (n=25); and second subgroup consisted of women receiving continue HRT schedule (0.625 mg conjugated estrogen+2.5 mg medroxyprogesterone acetate from days 1 to 28) for 2 months (n=25). Plasma TNFalpha, IL-1beta and IL-10 concentrations were measured with ELISA kits. Fasting urinary Hyp was measured by Ehrlich's spectrophotometric reaction. Ca was determined by oxalate precipitation and the redox titration procedure. Statistical significance was analysed by Kruskal-Wallis plus post hoc Mann-Whitney U-tests for multiple comparisons, Wilcoxon signed ranks test for paired data, and Pearson correlation test.
Compared with premenopausal individuals, postmenopausal women have increased plasma TNFalpha, IL-1beta, IL-10 (p<0.0001, p<0.0001, and p<0.001, respectively); and increased urinary Hyp and Ca concentrations (p<0.05). HRT (both cycle and continue schedules) lead to a significant decrease in TNFalpha, IL-1beta and urinary Hyp concentrations, and has no effect uppon IL-10 levels. HRT reverses increased urinary Hyp and Ca excretion to the premenopausal level. There is a significant positive correlation between pre- and post-HRT IL-1beta levels in both cycle and continue subgroups (r=0.437, p<0.05; and r=0.656, p<0.01, respectively), and between pre-HRT IL-1beta and urinary Ca (r=0.509, p<0.01; and r=0.415, p<0.05). There is a significant negative correlation between post-HRT IL-10 and TNFalpha levels in continue HRT receiving group (r=-0.446, p<0.05). Urinary Hyp in cycle and continue HRT received subgroups are correlated with post-treatment values (r=0.455, p<0.05; and r=0.776, p<0.01).
Plasma TNFalpha, IL-1beta, IL-10; and urinary Hyp and Ca increase with menopause. We suggest that the increase of IL-10 is secondary to the elevation of TNFalpha and IL-1beta and that the increase of IL-10 is a compensatory mechanism, by which this anti-inflammatory cytokine counteracts to pro-inflammatory TNFalpha and IL-1beta, and thus balances their osteoclast activating and oxidative stress-related effects. Two months duration HRT (cycle and continue schedule) lead to the significant decrease in plasma TNFalpha, IL-1beta and urinary Hyp concentrations. HRT reverses increased Hyp and Ca excretion to the premenopausal level. So, HRT, decreasing Th1 cytokines (TNFalpha, IL-1beta) probably improve the aberation of Th1/Th2 balance that is implicated in various pathological conditions. However, because of the relatively small number of participants and short duration of the therapy, further studies are necessary to establish a risk/benefit ratio for HRT to view effects on cytokine pattern and bone metabolism.
Tanshinone IIA, a diterpene quinone extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, is used widely and successfully in clinics in China for treating inflammatory diseases. Recently tanshinone IIA has been reported to have apoptosis inducing effects on a large variety of cancer cells. In this study, the anti-proliferation and apoptosis inducing effects of tanshinone IIA as well as its influence on cell adhesion to and invasion through the extracellular matrix (ECM) on acute promyelocytic leukemia (APL) NB4 cells in vitro were studied. Cell proliferation was assessed by MTT assay, cell apoptosis was observed by Hoechst 33258 staining and flow cytometry (FCM); The variation of caspase-3 and apoptotic related genes were assayed by Western blotting, cell mitochondrial membrane potential as well as cell adhesive and invasive effects were also investigated by using standard methods. The results showed that tanshinone IIA exhibited induction of apoptosis by activation of caspase-3, downregulation of anti-apoptotic protein bcl-2 and bcl-xl and upregulation of pro-apoptotic protein bax, as well as disruption of the mitochondrial membrane potential. Furthermore, treatment by tanshinone IIA could reduce cell adhesion to and invasion through ECM in leukemia NB4 cells. These data provide a potential mechanism for tanshinone IIA-induced apoptosis and cell growth inhibition in leukemia NB4 cells, suggesting that tanshinone IIA may serve as an effective adjunctive reagent for the treatment of APL.
Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties, cytotoxic activities against multiple human cancer cells, inducing apoptosis and differentiation of some human cancer cells. The purpose of this study is to confirm its anticancer activity on human glioma cells, and to elucidate mechanism of its activity. Human glioma cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation after treatment with tanshinone IIA. Its effect of apoptosis induction was detected through EB/AO staining, cell cycle analysis and the expressions of ADPRTL1 and CYP1A1 genes, the differentiation induction effect was investigated through morphology, mRNA and protein expressions of GFAP and nestin genes by RT-PCR and immunocytochemistry. Tanshinone IIA demonstrated a dose- and time-dependent inhibitory effect on cell growth, IC(50) was 100 ng/ml, and it significantly inhibited colony formation and BrdU incorporation of human glioma cells. After treatment with 25-100 ng/ml of tanshinone IIA, the apoptotic cells increased significantly (P < 0.01), the cells in G(0)/G(1) phase increased (P < 0.01), and decreased in S phase, ADPRTL1 and CYP1A1 mRNA expression increased 1-2 folds. The cells treated with 100 ng/ml tanshinone IIA demonstrated astrocytes or neuron-like morphology, GFAP mRNA and protein expressions increased, nestin mRNA and protein expressions decreased significantly. The findings in this study suggested that tanshinone IIA exhibited strong effects on growth inhibition and induction of apoptosis and differentiation in human glioma cells. It might serve as a novel promising differentiation-inducing and/or therapeutic agent for human gliomas, and need to be investigated further.
In this study, the antiviral activities of seven different extracts of Salvia miltiorrhiza (danshen) were determined. The first two extracts, SA1 and SA2, isolated at room temperature by ethyl acetate and water extraction, respectively, neutralized the enterovirus 71-induced cytopathic effect in Vero, rhabdomyosarcoma and MRC-5 cells. The other five crude extracts, extracted with warm water (60-70 degrees C) or organic solvents, did not have any protective activity. The 50% inhibitory concentrations for neutralizing the enterovirus 71-induced cytopathic effect were 0.742 +/- 0.042 mg/ml for SA1 and 0.585 +/- 0.018 mg/ml for SA2 in Vero cells. No antiviral activity was observed in the other viruses tested. Antiviral activity was more efficient in cultures treated with SA1 or SA2 during viral infection compared to the cultures treated before or after infection, suggesting that these danshen extracts could interfere with viral entry. SA1 and SA2 were able to inhibit viral RNA synthesis in the infected cells and to abate the apoptotic process in enterovirus 71-infected Vero cells. We conclude that danshen extracts possess antiviral activity and have potential for the development as an anti-enterovirus 71 agent.
Danshen is one of the most versatile Chinese herbal drugs that have been used for hundred of years in the treatment of numerous ailments. Because of its properties of improving microcirculation, causing coronary vasodilatation, suppressing the formation of thromboxane, inhibiting platelet adhesion and aggregation, and protecting against myocardial ischemia, it is widely used either alone or in combination with other herbal ingredients for patients with coronary artery disease and other cardiovascular diseases, in both China and other countries including the United States. This article provides an overview of its history, pharmacology, pharmacokinetics, clinical applications, side effects, interactions with Western drugs, and future prospects in the management of cardiovascular diseases.
Tanshinone IIA (tan), a derivative of phenanthrenequinone, is one of the key components of Salvia miltiorrhiza Bunge. Previous reports showed that tan inhibited the apoptosis of cultured PC12 cells induced by serum withdrawal or ethanol. However, whether tan has a cardioprotective effect against apoptosis remains unknown. In this study, we investigated the effects of tan on cardiac myocyte apoptosis induced both by in vitro incubation of neonatal rat ventricular myocytes with H(2)O(2) and by in vivo occlusion followed by reperfusion of the left anterior descending coronary artery in adult rats. In vitro, as revealed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, treatment with tan prior to H(2)O(2) exposure significantly increased cell viability. Tan also markedly inhibited H(2)O(2)-induced cardiomyocyte apoptosis, as detected by ladder-pattern fragmentation of genomic DNA, chromatin condensation, and hypodioloid DNA content. In vivo, tan significantly inhibited ischemia/reperfusion-induced cardiomyocyte apoptosis by attenuating morphological changes and reducing the percentage of terminal transferase dUTP nick end-labeling (TUNEL)-positive myocytes and caspase-3 cleavage. These effects of tan were associated with an increased ratio of Bcl-2 to Bax protein in cardiomyocytes, an elevation of serum superoxide dismutase (SOD) activity and a decrease in serum malondialdehyde (MDA) level. Taken together, these data for the first time provide convincing evidence that tan protects cardiac myocytes against oxidative stress-induced apoptosis. The in vivo protection is mediated by increased scavenging of oxygen free radicals, prevention of lipid peroxidation and upregulation of the Bcl-2/Bax ratio.
This study was conducted in an effort to evaluate the antimicrobial activity and antibiotic-resistant gene regulation from Saliva miltiorrhiza Bunge on methicillin-resistant Staphylococcus aureus (MRSA). A variety of solvent fractions and methanol extracts of S. miltiorrhiza Bunge were tested in order to determine its antimicrobial activities against S. aureus and MRSA. As a result, the hexane fraction of S. miltiorrhiza Bunge evidenced the highest levels of antimicrobial activity against S. aureus and MRSA. The MICs of the hexane fraction against various MRSA specimens were 64<MICs<or=128 microg/ml. The hexane fraction evidenced inhibitory effects superior to those of the chloroform fraction. The results showed inhibition zones of hexane (16 mm) and chloroform (14 mm) fractions against MRSA KCCM 40511 at 1,000 microg/disc. The hexane and chloroform fractions inhibited the expression of the resistant genes, mecA, mecR1, and femA in mRNA. Moreover, the results of Western blotting assays indicated that the hexane and chloroform fractions inhibited the expression of the resistant protein, PBP2a. These results reveal that the hexane and chloroform fractions of S. miltiorrhiza Bunge may prove to be a valuable choice for studies targeted toward the development of new antimicrobial agents.
Tanshinones are abietane type-diterpene quinones isolated from the roots of Radix Salvia miltiorrhiza (Danshen), a well-known traditional Chinese medicine in the treatment of cardiovascular diseases. Among the major diterpenes isolated, including cryptotanshinone, tanshinone I, tanshinone IIA and dihydrotanshinone, tanshinone IIA had been shown to posses various pharmacological activities including antioxidant, protection/prevention from angina pectoris and myocardial infarction, and anticancer properties. Tanshinone IIA, usually the most abundant tanshinone present in the herb, has been the focus of studies in its clinical potential, among which its ability to inhibit the proliferation of cancer cell lines. The aim of this study was to study the cytotoxicity of the tanshinones on human HepG2 cells in vitro in relation to intracellular glutathione perturbation (reduced glutathione, GSH and oxidized glutathione, GSSG). Studies using MTT assay showed that all tanshinones decreased cell viability of HepG2 cells in a concentration-dependent manner, with the cell viability decreased to 60% and 35% after 24 h and 48 h treatment, respectively. Assessment of apoptotic cells with fragmented DNA by flow cytometry indicated that only tanshinone IIA (12.5 and 25 microM) induced apoptosis in the cancer cells. Tanshinone IIA and cryptotanshinone caused significant decreases in G(1) cells by 23% and 13%, respectively, after 24 h treatment. The declines in G(1) cells were compensated by increases in G(2)/M (15% for tanshinone IIA) and S cells (8% and 13% for tanshinone IIA and cryptotanshinone, respectively). All the tanshinones studied, except tanshinone IIA, elevated GSH/GSSG ratio at low concentrations (1.56 and 3.13 microM), but the ratio decreased, indicating oxidative stress at high concentrations (6.25-25 microM). Taken together, tanshinone IIA caused HepG2 cytotoxicity through apoptosis without influencing oxidative stress, while the other tanshinones showed lower efficacy in inducing apoptosis in the HepG2 cells.
Ischemia and reperfusion (I/R) exerts multiple insults in microcirculation, frequently accompanied by endothelial cell injury, enhanced adhesion of leukocytes, macromolecular efflux, production of oxygen free radicals, and mast cell degranulation. Since the microcirculatory disturbance results in injury of organ involved, protection of organ after I/R is of great importance in clinic. Salvia miltiorrhiza root has long been used in Asian countries for clinical treatment of various microcirculatory disturbance-related diseases. This herbal drug contains many active water-soluble compounds, including protocatechuic aldehyde (PAl), 3,4-dihydroxyphenyl lactic acid (DLA) and salvianolic acid B (SalB). These compounds, as well as water-soluble fraction of S. miltiorrhiza root extract (SMRE), have an ability to scavenge peroxides and are able to inhibit the expression of adhesion molecules in vascular endothelium and leukocytes. Moreover, lipophilic compounds of SMRE also prevent the development of vascular damage; NADPH oxidase and platelet aggregation are inhibited by tanshinone IIA and tanshinone IIB, respectively, and the mast cell degranulation is blunted by cryptotanshinone and 15,16-dihydrotanshinone I. Thus, the water-soluble and lipophilic compounds of SMRE appear to improve the I/R-induced vascular damage multifactorially and synergically. This review will summarize the ameliorating effect of compounds derived from SMRE on microcirculatory disturbance and target organ injury after I/R and will provide a new perspective on remedy with multiple drugs.