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The structure of cryptotanshinone and tanshinone IIA from S. miltiorrhiza.
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In the course of screening of angiogenesis inhibitor from natural products, cryptotanshinone from Salvia miltiorrhiza was isolated as a potent small molecule inhibitor of angiogenesis. Cryptotanshinone inhibits bFGF-induced angiogenesis of BAECs at ten micromolar ranges in vitro without cytotoxicity. Tanshinone IIA, another tanshinone isolated from...
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... tanshinones were obtained as active principles from the CH2Cl2 extract of root of S. miltiorrhiza ba- sed on bioactivity-guided isolation of the inhibitory act- ivity against the proliferation of BAECs. These active compounds were identified as cryptotanshinone and tanshinone IIA (Figure 1), which belong to abietane diterpenes from the comparison of spectral data with published values ( Kang et al., 1997). As shown in Figure 1, the structural difference between cryptotan- shinone and tanshinone IIA is only the presence of double bond at C-15 position of furan ring. ...
Context 2
... active compounds were identified as cryptotanshinone and tanshinone IIA (Figure 1), which belong to abietane diterpenes from the comparison of spectral data with published values ( Kang et al., 1997). As shown in Figure 1, the structural difference between cryptotan- shinone and tanshinone IIA is only the presence of double bond at C-15 position of furan ring. ...
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Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza, has been shown to inhibit growth and induce apoptosis in various cancer cells. The association of its inhibitory effect on the primary malignant bone tumor, osteosarcoma, with mitochondrial dysfunction remains unclear. This study aimed to investigate the anti-p...
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... This is of extreme importance from the perspective of a selective blockade of the EP3 activity (and/or activation of EP2 or EP4) in view of rational strategies for developing novel antiplatelet agents and/or preventing thrombogenesis. All these findings are strengthened by the lack of toxic effects and by a low cytotoxic profile for tanshinones in both human and murine cell lines [125][126][127]. Moreover, recent reports have revealed that both TIIA and CRY are able to selectively induce apoptosis in different cancer cell lines in a concentration and time-dependent manner [128][129][130]. ...
Tanshinone IIA (TIIA) and cryptotanshinone (CRY) from Salvia miltiorrhiza Bunge were investigated for their inhibitory activity against the cyclooxygenase-2 (COX-2)/microsomal prostaglandin E synthase-1 (mPGES-1)/endothelial prostaglandin 3 (EP3) pathway using in silico, in vitro, in vivo, and ex vivo assays. From the analysis of the docking poses, both diterpenoids were able to interact significantly with COX-2, 5-lipoxygenase (5-LO), platelet-activating factor receptor (PAFR), and mPGES-1. This evidence was further corroborated by data obtained from a cell-free assay, where CRY displayed a significant inhibitory potency against mPGES-1 (IC50 = 1.9 ± 0.4 µM) and 5-LO (IC50 = 7.1 µM), while TIIA showed no relevant inhibition of these targets. This was consistent with their activity to increase mice bleeding time (CRY: 2.44 ± 0.13 min, p ≤ 0.001; TIIA: 2.07 ± 0.17 min p ≤ 0.01) and with the capability to modulate mouse clot retraction (CRY: 0.048 ± 0.011 g, p ≤ 0.01; TIIA: 0.068 ± 0.009 g, p ≤ 0.05). For the first time, our results show that TIIA and, in particular, CRY are able to interact significantly with the key proteins involved not only in the onset of inflammation but also in platelet activity (and hyper-reactivity). Future preclinical and clinical investigations, together with this evidence, could provide the scientific basis to consider these compounds as an alternative therapeutic approach for thrombotic- and thromboembolic-based diseases.
... CT and Tan IIA have similar structures except C-15 position of dihydrofuran ring. This might infer that the double bond at C-15 position of dihydrofuran ring contributed to the antiangiogenesis efficacy (Hur et al., 2005). In another research, CT inhibited tubular-like structure formation and decreased VEGF expression and LiCl-induced β-catenin augmentation in HUVECs. ...
Cancer is a common malignant disease worldwide with an increasing mortality in recent years. Salvia miltiorrhiza, a well-known traditional Chinese medicine, has been used for the treatment of cardiovascular and cerebrovascular diseases for thousands of years. The liposoluble tanshinones in S. miltiorrhiza are important bioactive components and mainly include tanshinone IIA, dihydrodanshinone, tanshinone I, and cryptotanshinone. Previous studies showed that these four tanshinones exhibited distinct inhibitory effects on tumor cells through different molecular mechanisms in vitro and in vivo. The mechanisms mainly include the inhibition of tumor cell growth, metastasis, invasion, and angiogenesis, apoptosis induction, cell autophagy, and antitumor immunity, and so on. In this review, we describe the latest progress on the antitumor functions and mechanisms of these four tanshinones to provide a deeper understanding of the efficacy. In addition, the important role of tumor immunology is also reviewed.
... In general, the plant-endophytic isolates were shown to produce a broad variety of exploitable metabolites, however, one particularly important compound, that was found to be also synthetized during axenic fermentation approaches in the present study, was cryptotanshinone. Previous studies showed that cryptotanshinone has antibacterial activity (Lee et al., 1999), inhibits angiogenesis (Hur et al., 2005) and inhibits STAT3 in prostate cancer (Shin et al., 2009). Moreover, it was previously reported that cryptotanshinone can be used for the treatment of coronary heart disease (Yu et al., 2009) and diabetes (Kim et al., 2007). ...
Endophytic fungi are often embedded in their host’s metabolic networks, which can result in alterations of metabolite production and higher amounts of active compounds in medicinal plants. This study reports the occurrence, diversity, and secondary metabolite profiles of endophytic fungi isolated from Salvia abrotanoides plants obtained from three geographically distinct sites in Iran. A total of 56 endophytic fungi were isolated from roots and leaves of S. abrotanoides; site-specificity and root-dominated colonization was found to be a general characteristic of the endophytes. Based on molecular identification, the endophytic fungi were classified into 15 genera. Mycelial extracts of these isolates were subjected to high-resolution mass spectrometry analyses and revealed a broad spectrum of secondary metabolites. Our results demonstrated that Penicillium canescens, P. murcianum, Paraphoma radicina, and Coniolariella hispanica are producers of cryptotanshinone, which is a main bioactive compound of S. abrotanoides. Moreover, it was shown that it can be produced independent of the host plant. The effect of exogenous gibberellin on S. abrotanoides and endophytic fungi was shown to have a positive effect on increasing the cryptotanshinone production in the plant as well as in endophytic fungi cultivated under axenic conditions. Our findings provide further evidence that endophytic fungi play an important role in the production plant bioactive metabolites. Moreover, they provide an exploitable basis to increase cryptotanshinone production in S. abrotanoides.
... Tanshinones are purified from the traditional Chinese herb Salvia miltiorrhiza Bunge (Danshen) and show various biological activities including angiogenic [22], anti-oxidant [23], and anti-inflammatory effects [24] and are effective against hepatocellular carcinoma [25]. Recent studies have reported that tanshinones can inhibit the growth of PCa cells and gastric cancer through cell death induction [26,27]. ...
Prostate cancer (PCa), an epithelial malignant tumor, is the second common cause of cancer death among males in western countries. Thus, the development of new strategies is urgently needed. Tanshinones isolated from Salvia miltiorrhiza and its synthetic analogs show various biological activities including anticancer effects. Among them, the tanshinone analog 2-((Glycine methyl ester)methyl)-naphtho (TC7) is the most effective, with better selectivity and lower toxicity. Therefore, in this work, the effect of TC7 against PCa was investigated through assessing the molecular mechanisms regulating the growth, metastasis, and invasion of PCa cells. Human PCa cells, PC3 and LNCAP, were used to evaluate TC7 mechanisms of action in vitro, while male BALB/c nude mice were used for in vivo experiments by subjecting each mouse to a subcutaneous injection of PC3 cells into the right flank to evaluate TC7 effects on tumor volume. Our in vitro results showed that TC7 inhibited cell proliferation by arresting the cell cycle at G2/M through the regulation of cyclin b1, p53, GADD45A, PLK1, and CDC2/cyclin b1. In addition, TC7 induced cell apoptosis by regulating apoptosis-associated genes such as p53, ERK1, BAX, p38, BCL-2, caspase-8, cleaved-caspase-8, PARP1, and the phosphorylation level of ERK1 and p38. Furthermore, it decreased DNA synthesis and inhibited the migration and invasion ability by regulating VEGF-1 and MMP-9 protein expression. Our in vivo evidence supports the conclusion that TC7 could be considered as a potential promising chemotherapeutic candidate in the treatment of PCa.
... The anti-angiogenic activities of Xanthohumol rely on repression of NF-jB, AKT and AMPK signaling pathways [83,85,86]. Other natural compounds have moderate inhibitory activity on CYP1 enzymes and were reported to restrain inflammation and angiogenesis, including antraquinones [90][91][92], naphthoquinones [93], tanshinones [94][95][96][97][98][99][100][101][102][103], flavonolignans [104][105][106][107][108][109] and triterpene acids [13,110,111]. ...
Cancer chemoprevention is the use of synthetic, natural or biological agents to prevent or delay the development or progression of malignancies. Intriguingly, many phytochemicals with anti-inflammatory and anti-angiogenic effects, recently proposed as chemoprevention strategies, are inhibitors of Cytochrome P450 family 1B1 (CYP1B1), an enzyme overexpressed in a wide variety of tumors and associated with angiogenesis. In turn, pro-inflammatory cytokines were reported to boost CYP1B1 expression, suggesting a key role of CYP1B1 in a positive loop of inflammatory angiogenesis. Other well-known pro-tumorigenic activities of CYP1B1 rely on metabolic bioactivation of xenobiotics and steroid hormones into their carcinogenic derivatives. In contrast to initial in vitro observations, in vivo studies demonstrated a protecting role against cancer for the other CYP1 family members (CYP1A1 and CYP1A2), suggesting that the specificity of CYP1 family inhibitors should be carefully taken into account for developing potential chemoprevention strategies. Recent studies also proposed a role of CYP1B1 in multiple cell types found within the tumor microenvironment, including fibroblasts, endothelial and immune cells. Overall, our review of the current literature suggests a positive loop between inflammatory cytokines and CYP1B1, which in turn may play a key role in cancer angiogenesis, acting on both cancer cells and the tumor microenvironment. Strategies aiming at specific CYP1B1 inhibition in multiple cell types may translate into clinical chemoprevention and angioprevention approaches.
... , COX-2, ER-í µí»¼, and ER-í µí»½ of both eutopic endometrium and ectopic endometrium tissues was performed using a twostep EnVision/HRP technique (Dako Cytomation, Denmark) according to the manufacturer's instruction as Hur et al reported [13]. Intensity and extent of staining was scored and five random fields were observed under a light microscope. ...
Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β-hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic.
... Benzofuran scaffold represents a promising structural core to discover a new class of active and selective angiogenesis inhibitors. It is known that dihydrobenzofuran scaffold actually exists in some anti-angiogenesis agents like cryptotanshinone [51], lignans [52] and A-3922 [53]. A series of benzofuran derivatives were synthesized and evaluated against HUVEC (Human umbilical vein endothelial cell) A549, Bel- 7402 and MCF-7 proliferation by Chen et al. [54]. ...
In nature's collection of biologically active heterocycles, benzofuran derivatives constitute a major group. The broad spectrum of pharmacological activity in individual benzofurans indicates that this series of compounds is of an undoubted interest. Benzofuran and its derivatives have attracted medicinal chemists and pharmacologists due to their pronounced biological activities and their potential applications as pharmacological agents. Due to the wide range of biological activities of benzofurans, their structure activity relationships have generated interest among medicinal chemists, and this has culminated in the discovery of several lead molecules in numerous disease conditions. The outstanding development of benzofuran derivatives in diverse diseases in very short span of time proves its magnitude for medicinal chemistry research. The present review is endeavour to highlight the progress in the various pharmacological activities of benzofuran derivatives in the current literature with an update of recent research findings on this nucleus.
... 12,13 Cryptotanshinone (CPT), one of the major representative components isolated from Danshen, has been reported to possess various pharmacological activities, such as anti-inflammatory, anti-angiogenic, anti-oxidative, anti-obese, and anti-diabetic functions. [14][15][16][17] Recently, CPT has also been reported to have obvious antitumor activity in a variety of cancer cells, including prostate carcinoma, hepatocarcinoma, rhabdomyosarcoma and melanoma cells. [18][19][20][21][22][23] In breast carcinoma cells, CPT has been shown to inhibit MCF7 cell proliferation by suppressing mTOR mediated CyclinD1 expression and Rb phosphorylation that lead to MCF7 cell apoptosis by inducing stress in the endoplasmic reticulum (ER). ...
Abstract Estrogen receptor (ER) is a major therapeutic target for the treatment of breast cancer, because of the crucial role of estrogen signaling deregulation in the development and progression of breast cancer. In this study, we report the identification of a novel ERα binding compound, cryptotanshinone (CPT), by screening the CADD database. We also show that CPT effectively inhibits estrogen-induced ER transactivation and gene expression of ER target genes. Furthermore, we showed that CPT suppressed breast cancer cell growth mainly in an ERα dependent manner. Finally, we confirmed the potential therapeutic efficiency of CPT using xenograft experiments in vivo. Taken together, our results describe a novel mechanism for the anticancer activity of CPT and provide supporting evidence for its use as a potential therapeutic agent to treat patients with ERα positive breast cancer.
... Cryptotanshinone, a kind of fat-soluble 2 terpenoids material [10] , has been isolated from the herb of Salvia miltiorrhiza and identified as the major chemical constituent [11]. Its molecular formula is C 19 H 20 O 3 , the Mol. ...
Objective. To explore the effect of Cryptotanshinone on reversing the reproductive and metabolic disturbances in polycystic ovary syndrome (PCOS) model rats and the possible regulatory mechanisms. Methods. PCOS model rats were induced by subcutaneous injection of dehydroepiandrosterone (DHEA) and verified by histological screening of vaginal exfoliated cells. After Cryptotanshinone intervention, the rats' body weight and ovary morphological were observed; the serum biochemical assessments were analyzed by radioimmunoassay (RIA) and key genes and proteins related with anabolism of androgen and insulin were detected by Real-Time PCR and Immunohistochemical (IHC). Results. The estrous cyclicity of PCOS model rats was significantly recovered by Cryptotanshinone. The body weight, ovarian coefficient, and ovarian morphology had been improved and the serum biochemical indicators including testosterone (T), androstenedione (A2), luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), sexual binding globulin (SHBG), low density cholesterol (LDL-C), fasting insulin (FINS) were reversed after Cryptotanshinone intervention. Specifically, the levels of Cytochrome P450, 17-a hydroxylase/17,20 lyase (CYP17), and androgen receptor (AR) were downregulated significantly. Conclusions. Our data suggest that Cryptotanshinone could rebalance reproductive and metabolic disturbances in PCOS model rats and could be a potential therapeutic agent for the treatment of PCOS.
... Salvia miltiorrhiza Bunge (Danshen) is an herb commonly used in traditional oriental medicine the treatment of several pathologies including cardiovascular diseases, hepatitis, menstrual disorders, diabetes, and chronic renal failure [14][15][16][17]. Cryptotanshinone (CT) is one of the principal active constituents in Danshen extract and has several pharmacological effects, such as anti-inflamma-tory, anti-oxidative, anti-bacterial, anti-angiogenic, antimutagenic, anti-platelet aggregation, anti-human hepatocellular carcinoma effects, and anti-cyclooxygenase-2 (COX-2) functions [18][19][20][21][22][23]. CT exhibits antimicrobial activity against a broad range of Gram-positive, including S. aureus, and Gram-negative bacteria as well as other microorganisms [24]. ...
