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Protective effects of Sal-B from Salvia bowleyana Dunn on oxidative DNA damage induced by AAPH. Lane 1, native DNA; lane 2, DNA treated with AAPH and solvent; lane 3, DNA treated with AAPH and 0.004 mmol/l Sal-B; lane 4-7, DNA treated with AAPH and 0.017, 0.03, 0.06 and 0.13 mmol/l Sal-B, respectively; lane 8, DNA treated with AAPH and 0.08 mmol/l rutin. A total of 100 ng pUC18 DNA and 12.5 mmol/l AAPH were used in every appropriate lane. Sal-B, salvianolic acid B; AAPH, 2,2'-azobis (2-methylpropionamidine) dihydrochloride; superco, supercoiled.
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Salvianolic acid B (Sal-B) is widely used in China for the treatment of numerous diseases. Currently, Salvia miltiorrhiza Bunge is the main source of this compound, but Salvia bowleyana Dunn, a surrogate of S. miltiorrhiza Bge, may provide a novel source for obtaining more Sal-B. In the present study, a simple method for separation and purification...
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... the ability of Sal-B from S. bowleyana Dunn to prevent oxidative DNA damage was examined (Fig. 6). It was observed that oxidative DNA damage was gradually diminished with increasing Sal-B concentration. Oxidative DNA damage was rarely observed at 0.06 mmol/l Sal-B; this concentration may effectively prevent DNA from being sheared. To some extent, the low level of apoptosis may be associated with the protective effect of Sal-B on ...
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... Previous studies have demonstrated the ability of Sal B to modulate the expression of various antioxidant enzymes in vivo, including SOD, GSH-Px, Grx1, and HO-1, effectively preventing NAD+ depletion and ROS generation [10,11]. Consequently, investigations into the anticancer properties of Sal B have revealed promising results indicating its potential in attenuating oxidative stress-induced progression of head and neck squamous cell carcinoma (HNSCC) cells as well as breast cancer cells [12][13][14][15][16][17]. Moreover, Han et al. demonstrated that Sal B not only induced apoptosis in A549 cells but also counteracted the reduction in cleaved caspase-3 levels typically induced by the apoptosis inhibitor TGF-β1 [18]. ...
Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD⁺. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD⁺/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.
... Previous studies have demonstrated the ability of Sal B to modulate the expression of various antioxidant enzymes in vivo, including SOD, GSH-Px, Grx1, and HO-1, effectively preventing NAD+ depletion and ROS generation [10,11]. Consequently, investigations into the anticancer properties of Sal B have revealed promising results indicating its potential in attenuating oxidative stress-induced progression of head and neck squamous cell carcinoma (HNSCC) cells as well as breast cancer cells [12][13][14][15][16][17]. Moreover, Li et al. (2014) reported that Sal B could inhibit NSCLC A549 cell growth in vitro with an IC50 value of approximately 279.6 µM by disrupting cyclooxygenase-2 (COX-2) activity [18], suggesting a potential therapeutic role for Sal B in NSCLC treatment. ...
Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase 3 (an apoptosis marker) and E-cadherin (a metastasis marker). Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD ⁺ . Additionally, a xenograft model with transplanted A549 tumors was employed to assess the antitumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD ⁺ /NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.
... Therefore, research and development of new drugs are key to improving drug efficacy and prolonging patient survival. Chen et al. (2020) reported that Sal-B decreases tumor cell viability, promotes ROS production, induces apoptosis, as well as reduces migration, invasion, and EMT of AGS and AGS/DDP cells. Sal-B also regulates proliferation, EMT, and apoptosis to reduce the resistance to DDP via the AKT/mTOR pathway in DDP-resistant gastric cancer cells (Wang et al., 2021) (Figure 1). ...
Salvia miltiorrhiza Bunge (Lamiaceae) is a perennial herb widely found in China since ancient times with a high economic and medicinal value. Salvianolic acid B (Sal-B) is an important natural product derived from Salvia miltiorrhiza and this review summarizes the anticancer activity of Sal-B. Sal-B inhibits tumor growth and metastasis by targeting multiple cell signaling pathways. This review aims to review experimental studies to describe the possible anticancer mechanisms of Sal-B and confirm its potential as a therapeutic drug.
... The activity of SM is a result of lipophilic compounds, including tanshinones and cryptotanshinones, and hydrophilic phenolic acids, including salvianolic acid a (Sal a) and salvianolic acid B (Sal B) (5). Sal B has the highest content of the aforementioned compounds in SM. it has been reported to be a potential cytotoxic polyphenol and is therefore a potential therapeutic in a number of different cancers, including, hepatocellular carcinoma, breast cancer, head and neck squamous cell carcinoma, gastric cancer and colorectal cancer, based on laboratory data (6)(7)(8)(9)(10)(11). Furthermore, Sal B was observed to inhibit nSclc a549 cell growth; its half maximal inhibitory ...
Salvianolic acid B (Sal B) is a potential cytotoxic polyphenol against cancer. In the present study the effect of Sal B and its molecular mechanism were investigated in the non‑small cell lung cancer (NSCLC) A549 cell line. The TGF‑β/MAPK/Smad signaling axis was explored. A549 cells were co‑cultured with and without different concentrations of Sal B (25, 50 and 100 µM respectively) and TGF‑β1 (9 pM) for 24 h. Cell epithelial‑mesenchymal transition (EMT), cell migration, cell cycle distribution, autophagy and apoptosis were assessed by western blotting (WB), wound healing assay and flow cytometry, respectively. Moreover, activation of MAPK, Smad2/3 and the downstream target, plasminogen activator inhibitor 1 (PAI‑1), were assessed by WB. The results demonstrated that Sal B inhibited TGF‑β1‑induced EMT and migration of A549 cells, hampered cell cycle progression and induced cell autophagy and apoptosis. Furthermore, Sal B inactivated MAPK signaling pathways and the phosphorylation of Smad2/3, especially the phosphorylation of Smad3 at the linker region, which resulted in decreased protein expression levels of PAI‑1 in TGF‑β1‑stimulated A549 cells. Overall, these results demonstrated that Sal B may have a potential therapeutic effect against NSCLC in vitro. The results of the present study indicated that the underlying active mechanism of Sal B in NSCLC may be closely related to the impeded activation of the MAPK and Smad2/3 signaling pathways. Therefore, Sal B may be a potential candidate NSCLC therapeutic agent.
... Chinese medicinal plant with a broad range of therapeutic effects. It has a thick main root and may be used as a substitute for Chinese sage (Salvia miltiorrhiza) (Figure 1) (Xu et al., 2016a;Chen et al., 2020). Salvia bowleyana and S. miltiorrhiza have similar morphologies and belong to the genus Salvia Linn from the Lamiaceae (Labiatae). ...
... Salvia bowleyana and S. miltiorrhiza are traditional Chinese medicinal plants the extracts of which promote blood circulation, remove blood stasis, eliminate troubles and relieve dysmenorrhea due to their high sal B content. Accordingly, they are good plant materials in which to explore sal B biosynthesis (Shi et al., 2007;Li et al., 2016;Chen et al., 2020). The S. miltiorrhiza genome was previously assembled into many small contigs or scaffolds (Xu et al., 2016a) and shown to encode 30,478 protein-coding genes. ...
Salvia bowleyana is a traditional Chinese medicinal plant that is a source of nutritional supplements rich in salvianolic acid B and a potential experimental system for the exploration of salvianolic acid B biosynthesis in the Labiatae. Here, we report a high‐quality chromosome‐scale genome assembly of S. bowleyana covering 462.44 Mb, with a scaffold N50 value of 57.96 Mb and 44,044 annotated protein‐coding genes. Evolutionary analysis revealed an estimated divergence time between S. bowleyana and its close relative S. miltiorrhiza of ~3.94 million years. We also observed evidence of a whole‐genome duplication in the S. bowleyana genome. Transcriptome analysis showed that SbPAL1 (PHENYLALANINE AMMONIA‐LYASE1) is highly expressed in roots relative to stem and leaves, paralleling the location of salvianolic acid B accumulation. The laccase gene family in S. bowleyana outnumbered their counterparts in both S. miltiorrhiza and Arabidopsis thaliana, suggesting that the gene family has undergone expansion in S. bowleyana. Several laccase genes were also highly expressed in roots, where their encoded proteins may catalyze the oxidative reaction from rosmarinic acid to salvianolic acid B. These findings provide an invaluable genomic resource for understanding salvianolic acid B biosynthesis and its regulation, and will be useful for exploring the evolution of the Labiatae.
... SAA, SAB, and SAC, which are major bioactive constituents of S. miltiorrhiza have been reported to have anticancer, anti-inflammatory, and cardioprotective effects. [13][14][15][16] S. miltiorrhiza exhibits inhibitory effects against hepatitis B, hepatitis C, and SARS-CoV viruses. [17][18][19] Although no drug has been confirmed to be effective in inhibiting 2019-nCoV, treatment of COVID-19 symptoms is still remarkable in clinic. ...
Since December 2019, the new coronavirus [also known as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2, 2019‐nCoV)]‐ induced disease, COVID‐19, has spread rapidly worldwide. Studies have reported that the traditional Chinese medicine Salvia miltiorrhiza possesses remarkable antiviral properties; however, the anti‐coronaviral activity of its main components, salvianolic acid A (SAA), salvianolic acid B (SAB), and salvianolic acid C (SAC) is still debated. In this study, we used Cell Counting Kit‐8 staining and flow cytometry to evaluate the toxicity of SAA, SAB, and SAC on ACE2 (angiotensin‐converting enzyme 2) high‐expressing HEK293T cells (ACE2h cells). We found that SAA, SAB and SAC had a minor effect on the viability of ACE2h cells at concentrations below 100 μM. We further evaluated the binding capacity of SAA, SAB, and SAC to ACE2 and the spike protein of 2019‐nCoV using molecular docking and surface plasmon resonance (SPR). They could bind to the receptor‐binding domain (RBD) of the 2019‐nCoV with a binding constant (KD) of (3.82±0.43) e‐6 M, (5.15±0.64)e‐7 M, and (2.19±0.14)e‐6 M; and bind to ACE2 with KD (4.08±0.61)e‐7 M, (2.95±0.78)e‐7 M and (7.32±0.42)e‐7M, respectively. As a result, SAA, SAB, and SAC were determined to inhibit the entry of 2019‐nCoV Spike pseudovirus with EC50 of 11.31μM, 6.22 μM, and 10.14 μM on ACE2h cells, respectively. In conclusion, our study revealed that three Salvianolic acids can inhibit the entry of 2019‐nCoV spike pseudovirus into ACE2h cells by binding to the RBD of the 2019‐nCoV spike protein and ACE2 protein.
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Background: Salvia bowleyana, S. splendens, and S. officinalis are globally distributed and have been widely used to treat coronary heart disease, liver tumors, and viral diseases. To systematically determine their phylogenetic relationship and develop molecular markers for species determination, we sequenced and assembled their chloroplast genomes, and analyzed the genome characteristics. Moreover, we compared the phylogenetic specification and divergence genes fragments of chloroplast genomes from the three Salvia species.
Results: The length of S. bowleyana, S. splendens, and S. officinalis chloroplast genomes were 151387 bp, 150604 bp, and 151163 bp, respectively. The sizes of the large-single copy, small-single copy, and inverted repeat regions were 82772 bp, 17573 bp, and 51042 bp for S. bowleyana; 82181 bp, 17857 bp, and 50566 bp for S. splendens; 82429 bp, 17510 bp, and 51224 bp for S. officinalis, respectively. The GC contents of the three chloroplast genomes were 38.01%, 38.04%, 38.04%, partly. In the comparison of chloroplast genomes from Lamiaceae family, the six genes ndhB, rpl2, rpl23, rps7, rps12, and ycf2 were present in the IRs regions of all 41 chloroplast genomes in the Lamiaceae family. We found that one of the gene rpl20 was intact and stably occurred in all 41 species chloroplast genomes, however, another pseudogene one was lost in that of 40 species except the Dracocephalum heterophyllum. For the repeat analysis, 29 tandem repeats, 35, 29, 24 simple-sequence repeats(SSRs), and 47, 49, 40 interspersed repeats were identified in the three Salvia species chloroplast genomes based on the diverse requirements. The three specific intergenic sequences(IGS) of rps16-trnQ-UUG, trnL-UAA-trnF-GAA, and trnM-CAU-atpE were found to discriminate the certain species by comparing 23 Salvia chloroplast genomes. Six genes including rpl22, rps19, rpl2, ycf1, ndhF, and psbA were found in the highly diverse IR boundary regions. The genetic distance analysis of IGS showed the trnL-UAG-ccsA, rps16-trnQ-UUG, ccsA-ndhD, rps15-ycf1, and ndhE-ndhG regions had the higher variability. Furthermore, the phylogenetic tree inferred that the 23 Salvia species formed a monophyletic group. Lastly, two pairs of Genus-specific DNA barcode primers were identified, which can be used to amplify the part sequence of trnM-CAU-atpE and ccsA-ndhD region.
Conclusions: We acquired the complete chloroplast genome of the three Salvia species, which will provide a solid foundation to understand their phylogenetic status in Salvia genus. Moreover, the research can provide the probability to discriminate the Salvia species compared with the genomics between the phenotype and the distinction of gene fragments .
The root of Salvia bowleyana Dunn (Lamiaceae) is used as a traditional Chinese medicine that has multiple therapeutic effects. In this study, an efficient strategy was developed to separate diterpenoid compounds, which are the main active ingredients in Salvia bowleyana Dunn roots, from complex crude extracts by high‐speed counter‐current chromatography combined with preparative high‐performance liquid chromatography. A two‐phase solvent system comprising n‐hexane‐ethyl acetate‐methanol‐water (7:3:7:3, v/v) was selected for high‐speed counter‐current chromatographic separation. Three major diterpenoids, 6α‐hydroxysugiol (7), sugiol (8), and 6, 12‐dihydroxyabieta‐5,8,11,13‐tetraen‐7‐one (9) were obtained at purities of 98.9%, 95.4%, and 96.2%, respectively, and minor diterpenoids were enriched via one‐step separation. The enriched minor diterpenoids were further purified by continuous preparative high‐performance liquid chromatography to yield two new norabietanoids (1, 6) and four known compounds (2–5). The structures of these new compounds were determined using nuclear magnetic resonance spectroscopy, high‐resolution electrospray ionisation mass spectrometry, and electronic circular dichroism spectroscopy. The results suggest that high‐speed counter‐current chromatography combined with preparative high‐performance liquid chromatography efficiently isolates diterpenoids, including minor components, from complex natural products. This article is protected by copyright. All rights reserved
Background
Cadmium (Cd) poses threats to human health by affecting the safety (Cd accumulation) and quantity (contents of active ingredients) of Salvia miltiorrhiza due to human activities and Cd characteristics. It remains largely unknown how Cd stress affects the synthesis of active ingredients in S. miltiorrhiza.
Results
Here we investigated physiologies (contents of Cd, malondialdehyde (MDA) and proline, and activities of superoxide dismutase, peroxidase (POD) and catalase (CAT)), transfer factor (TF), bioconcentration factor (BCF) and metabolites of S. miltiorrhiza at different levels of Cd contamination with a pot experiment. The results revealed that Cd concentration, as it rose in soil, increased significantly in roots and leaves with TFs and BCFs below 1 in the Cd addition groups; POD and CAT activities and proline content increased and then declined significantly. Besides, amino acids and organic acids (especially D-glutamine (D-Gln), L-aspartic acid (L-Asp), L-phenylalanine (L-Phe), L-tyrosine (L-Try), geranylgeranyl-PP (GGPP), and rosmarinic acid (RA)) contributed more than other metabolites in discriminating roots under different levels of Cd contamination. With Cd concentration rising, the relative content of GGPP declined and then increased significantly; RA content rose significantly; content of L-Phe and L-Try increased and then declined significantly, while the content of D-Gln and L-Try decreased and then increased significantly.
Conclusions
These results suggested that S. miltiorrhiza belonged to a non-Cd-hyperaccumulator with most Cd accumulated in roots; Cd enhanced the RA synthesis via regulating amino acid metabolism but inhibited the tanshinone synthesis mainly by declining the GGPP content, with proline, POD and CAT playing vital roles in resisting Cd stress.
