Pharmacological effects of Salvia miltiorrhiza (Danshen) on cerebral infarction.
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ABSTRACT:
SUBMITTER: Lin TH
PROVIDER: S-EPMC2910010 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Heart failure (HF) represents a major public health burden. Inflammation has been shown to be a critical factor in the progression of HF, regardless of the aetiology. Disappointingly, the majority of clinical trials targeting aspects of inflammation in patients with HF have been largely negative. Many clinical researches demonstrate that danshen has a good efficacy on HF, and however, whether danshen exerts anti-inflammatory effects against HF remains unclear. In our study, the employment of a water extracted and alcohol precipitated of danshen extract attenuated cardiac dysfunction and inflammation response in acute myocardial infarction-induced HF rats. Transcriptome technique and validation results revealed that TLR4 signalling pathway was involved in the anti-inflammation effects of danshen. In vitro, danshen reduced the release of inflammatory mediators in LPS-stimulated RAW264.7 macrophage cells. Besides, the LPS-stimulated macrophage conditioned media was applied to induce cardiac H9C2 cells injury, which could be attenuated by danshen. Furtherly, knock-down and overexpression of TLR4 were utilized to confirm that danshen ameliorated inflammatory injury via MyD88-dependent TLR4-TRAF6-NF-κB signalling pathway in cardiomyocytes. Furthermore, by utilizing co-immunoprecipitation, danshen was proved to suppress MD2/TLR4 complex formation and MyD88 recruitment. In conclusion, our results demonstrated that danshen ameliorates inflammatory injury by controlling MD2/TLR4-MyD88 complex formation and TLR4-TRAF6-NF-κB signalling pathway in acute myocardial infarction-induced HF.
| S-EPMC7521313 | biostudies-literature
Project description:Danshen (Salvia miltiorrhiza) is a well-known herb in Traditional Chinese Medicine (TCM) for treating cardiovascular diseases, but the underlying mechanism remains to be fully elucidated. Here, we showed that Danshen and its active ingredient rosmarinic acid exhibited antiplatelet effects through the inhibition of ERp57, a member of protein disulfide isomerase (PDI) with potential roles in platelet aggregation. Danshen extract (DSE) exhibited potent inhibitory effects on the platelet aggregation induced by arachidonic acid- (AA-) induced platelet aggregation and the enzymatic activity of ERp57. Rosmarinic acid was identified by virtual screening and molecular docking as one of the hit compounds for ERp57. In line with this, rosmarinic acid displayed significant inhibitory effect on ERp57 activity and inhibited AA-induced platelet aggregation. Taken together, we demonstrated for the first time that DSE and rosmarinic acid displayed inhibitory effects on the catalytic activity of ERp57, providing evidence of the regulatory role of ERp57 underlying the antiplatelet effects of Danshen.
| S-EPMC5941821 | biostudies-literature
Project description:Danshen was able to reduce the risk of the patients with coronary heart disease (CHD), but the mechanism is still widely unknown. Biochemical indices (lipid profile, markers of renal and liver function, and homocysteine (Hcy)) are closely associated with CHD risk. We aimed to investigate whether the medicine reduces CHD risk by improving these biochemical indices. The patients received 10 Danshen pills (27?mg/pill) in Dashen group, while the control patients received placebo pills, three times daily. The duration of follow-up was three months. The serum biochemical indices were measured, including lipid profiles (LDL cholesterol (LDL-C), HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein (Apo) A, ApoB, ApoE, and lipoprotein (a) (Lp(a))); markers of liver function (gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), indirect bilirubin (IBil), and direct bilirubin (DBil)); marker of renal function (uric acid (UA)) and Hcy. After three-month follow-up, Danshen treatment reduced the levels of TG, TC, LDL-C, Lp(a), GGT, DBil, UA, and Hcy (P < 0.05). In contrast, the treatment increased the levels of HDL-C, ApoA, ApoB, ApoE, TBil, and IBil (P < 0.05). Conclusion. Danshen can reduce the CHD risk by improving the biochemical indices of CHD patients.
| S-EPMC4913020 | biostudies-other
Project description:BACKGROUND:Danshen (Salvia miltiorrhiza Bunge), also known as Chinese red sage, is a member of Lamiaceae family. It is valued in traditional Chinese medicine, primarily for the treatment of cardiovascular and cerebrovascular diseases. Because of its pharmacological potential, ongoing research aims to identify novel bioactive compounds in danshen, and their biosynthetic pathways. To date, only expressed sequence tag (EST) and RNA-seq data for this herbal plant are available to the public. We therefore propose that the construction of a reference genome for danshen will help elucidate the biosynthetic pathways of important secondary metabolites, thereby advancing the investigation of novel drugs from this plant. FINDINGS:We assembled the highly heterozygous danshen genome with the help of 395?×?raw read coverage using Illumina technologies and about 10?×?raw read coverage by using single molecular sequencing technology. The final draft genome is approximately 641 Mb, with a contig N50 size of 82.8 kb and a scaffold N50 size of 1.2 Mb. Further analyses predicted 34,598 protein-coding genes and 1,644 unique gene families in the danshen genome. CONCLUSIONS:The draft danshen genome will provide a valuable resource for the investigation of novel bioactive compounds in this Chinese herb.
| S-EPMC4678694 | biostudies-literature
Project description:The roots of Salvia miltiorrhiza ("Danshen") have been used in Chinese herbal medicine for centuries for a host of different conditions. While the exact nature of the active components of this material are unknown, large amounts of tanshinones are present in extracts derived from these samples. Recently, the tanshinones have been demonstrated to be potent human carboxylesterase (CE) inhibitors, with the ability to modulate the biological activity of esterified drugs. During the course of these studies, we also identified more active, irreversible inhibitors of these enzymes. We have purified, identified, and synthesized these molecules and confirmed them to be the anhydride derivatives of the tanshinones. These compounds are exceptionally potent inhibitors ( Ki < 1 nM) and can inactivate human CEs both in vitro and in cell culture systems and can modulate the metabolism of the esterified drug oseltamivir. Therefore, the coadministration of Danshen extracts with drugs that contain the ester chemotype should be minimized since, not only is transient inhibition of CEs observed with the tanshinones, but also prolonged irreversible inhibition arises via interaction with the anhydrides.
| S-EPMC6263802 | biostudies-literature
Project description:The roots of Salvia miltiorrhiza are the source of the traditional Chinese medicine danshen and the class of tanshinones, particular quinoid nor-diterpenoids of the abietane type. Of these compounds, cryptotanshinone, dihydrotanshinone I, tanshinone I, and tanshinone IIA, have been extensively studied for their anticancer potential, not only but as well because of their high abundance in S. miltiorrhiza and their thus easy availability. However, also additional Salvia species are known to contain tanshinones, mainly such of the subgenus Glutinaria, of which S. glutinosa is the only species widely occurring in Europe. Using UHPLC-DAD-MS, the tanshinone profile of S. glutinosa roots collected from two different locations was compared to the profile in S. miltiorrhiza roots. In addition, tanshinone IIA and another six diterpenoids from S. glutinosa were investigated for their antiproliferative and cytotoxic potential against MDA-MB-231 and HL-60 cells. Apart from dihydrotanshinone I, which has been previously characterized due to its anticancer properties, we determined danshenol A as a highly antiproliferative and cytotoxic agent, significantly surpassing the effects of dihydrotanshinone I. With regard to the diterpenoid profile, S. miltiorrhiza showed a higher concentration for most of the tanshinones, except for (+)-danshexinkun A, which was present in comparable amounts in both species. Danshenol A, in contrast, was only present in S. glutinosa as were dehydroabietic acid and (+)-pisiferic acid. The results of our study underlines the long traditional use of danshen due to its high amount on tanshinones, but also demonstrates the potential value of investigating closely related species for the discovery of new biologically active lead compounds.
| S-EPMC10729661 | biostudies-literature
Project description:Four novel compounds (1-4) as well as fourteen reported compounds (5-18) were isolated and purified from Salvia miltiorrhiza Bunge (Danshen). The structures of novel compounds were determined by 1D and 2D NMR, HRESIMS data, etc. The anti-inflammatory properties of all the compounds on RAW264.7 macrophages and their cytotoxicity on H1299 and Bel-7402 cell lines coupled with a structure-activity relationship (SAR) were investigated. Compound 4 demonstrated the best anti-inflammatory activity and was chosen for further research. Compound 4 greatly suppressed secretion of nitric oxide (NO), tumor necrosis factor (TNF)-? and interleukin-6 (IL-6) in the RAW264.7 macrophages stimulated by LPS. Additionally, the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased and the nuclear translocation of NF-?B was attenuated after treatment with compound 4 in vitro. Compound 4 was able to dramatically inhibit LPS-induced activation of JNK1/2 and ERK1/2 and remarkably disrupted the TLR4 dimerization in LPS-induced RAW264.7 macrophages. Thus, the new compound 4 suppressed LPS-induced inflammation partially is due to the blocking TLR4 dimerization. In addition, the anti-cancer activity investigation indicated that most of isolated compounds exhibited cytotoxicity and the SAR analysis showed that the intact D ring was indispensable and unsaturated D ring played vital role.
| S-EPMC5036060 | biostudies-literature
Project description:Background: Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae) is commonly used in Asia, including China, Japan, and Korea with markets in America and Europe growing substantially. It is included in multiple pharmacopeias and salvianolic acid B and tanshinone IIA are used as quality markers. However, on the markets, substitutes and different processing methods often are a concern. a concern regarding patients' safety and expected outcomes. Aims: This study aims at understanding the quality of Danshen-derived products on the market, and the relationship between the chemistry, biological activity and the processing and storage methods. Methods: For heavy metal analysis, inductively coupled plasma optical emission spectrometry was used. High performance thin-layer chromatography and proton nuclear magnetic resonance coupled with principal component analysis were used to understand the variation of metabolite composition. MTT assay and LPS induced NO production assay were used to evaluate the cytotoxicity effect and anti-inflammatory activity, respectively. Result and Discussion: Six out of sixty samples exceed the limits of cadmium according to the Chinese or United States Pharmacopoeia. Arsenic, lead and copper contents are all below pharmacopoeial thresholds. With more complex processing procedure, the risk of heavy metal contamination increases, especially with arsenic and cadmium. The metabolite compositions show a variability linked to processing and storage methods. Authenticated samples and Vietnamese primary samples contain higher salvianolic acid B, and their chemical compositions are more consistent compared to Chinese online store samples. Overall, a significant chemical variation can be observed in Danshen products directly linked to processing and storage method. In the MTT assay, fourteen samples show cytotoxicity while seven samples increase the proliferation of RAW264.7. In the LPS induced NO production of RAW 264.7, only seven samples show significant inhibitory effects. Conclusion: This is the first interdisciplinary investigation focusing on understanding the current market and the quality of Danshen. The quality of Danshen products on the high street are inferior to the authenticated samples. The results of the bioassays selected is not useful to differentiate the quality and composition according to the current definition in the pharmacopoeias. Overall, this approach highlights the tremendous variability of the products linked to processing and the need for more systematic and stringent quality assurance.
| S-EPMC8107819 | biostudies-literature
Project description:AimTanshinol is an important catechol in the antianginal herb Salvia miltiorrhiza roots (Danshen). This study aimed to characterize tanshinol methylation.MethodsMetabolites of tanshinol were analyzed by liquid chromatography/mass spectrometry. Metabolism was assessed in vitro with rat and human enzymes. The major metabolites were synthesized for studying their interactions with drug metabolizing enzymes and transporters and their vasodilatory properties. Dose-related tanshinol methylation and its influences on tanshinol pharmacokinetics were also studied in rats.ResultsMethylation, preferentially in the 3-hydroxyl group, was the major metabolic pathway of tanshinol. In rats, tanshinol also underwent considerable 3-O-sulfation, which appeared to be poor in human liver. These metabolites were mainly eliminated via renal excretion, which involved tubular secretion mainly by organic anion transporter (OAT) 1. The methylated metabolites had no vasodilatory activity. Entacapone-impaired methylation did not considerably increase systemic exposure to tanshinol in rats. The saturation of tanshinol methylation in rat liver could be predicted from the Michaelis constant of tanshinol for catechol-O-methyltransferase (COMT). Tanshinol had low affinity for human COMT and OATs; its methylated metabolites also had low affinity for the transporters. Tanshinol and its major human metabolite (3-O-methyltanshinol) exhibited negligible inhibitory activities against human cytochrome P450 enzymes, organic anion transporting polypeptides 1B1/1B3, multidrug resistance protein 1, multidrug resistance-associated protein 2, and breast cancer resistance protein.ConclusionTanshinol is mainly metabolized via methylation. Tanshinol and its major human metabolite have low potential for pharmacokinetic interactions with synthetic antianginal agents. This study will help define the risk of hyperhomocysteinemia related to tanshinol methylation.
| S-EPMC4422947 | biostudies-literature
Project description:BackgroundThe dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known, traditional Chinese medicine. Tanshinones are active compounds that accumulate in the periderm, resulting in red-colored roots. However, lines with orange roots have been observed in cultivated fields. Here, we performed metabolome and transcriptome analyses to investigate the changes of orange-rooted Danshen.MethodsMetabolome analysis was performed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof-MS) to investigate the metabolites variation between orange Danshen and normal Danshen. RNA sequencing and KEGG enrichment analysis were performed to analyzing the differentially expressed genes between orange-rooted and normal Danshen.ResultsIn total, 40 lipophilic components were detected in metabolome analysis, and seven compounds were significantly decreased in the orange Danshen, including the most abundant active compounds, tanshinone IIA and tanshinone I in normal Danshen. Systematic analysis of transcriptome profiles revealed that the down-regulated genes related to catalytic dehydrogenation was not detected. However, two genes related to stress resistance, and four genes related to endoplasmic reticulum (ER)-associated degradation of proteins were up-regulated in orange Danshen.ConclusionsDecreases in the content of dehydrogenated furan ring tanshinones such as tanshinone IIA resulted in phenotypic changes and quality degradation of Danshen. Transcriptome analysis indicated that incorrect folding and ER-associated degradation of corresponding enzymes, which could catalyze C15-C16 dehydrogenase, might be contributed to the decrease in dehydrogenated furan ring tanshinones, rather than lower expression of the relative genes. This limited dehydrogenation of cryptotanshinone and dihydrotanshinone I into tanshinones IIA and I products, respectively, led to a reduced quality of Danshen in cultivated fields.
| S-EPMC6775661 | biostudies-literature