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1.
Int J Mol Sci ; 22(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502445

RESUMO

The dried root of Salvia miltiorrhiza is a renowned traditional Chinese medicine that was used for over 1000 years in China. Salvianolic acid B (SalB) is the main natural bioactive product of S. miltiorrhiza. Although many publications described the regulation mechanism of SalB biosynthesis, few reports simultaneously focused on S. miltiorrhiza root development. For this study, an R2R3-MYB transcription factor gene (SmMYB52) was overexpressed and silenced, respectively, in S. miltiorrhiza sterile seedlings. We found that SmMYB52 significantly inhibited root growth and indole-3-acetic acid (IAA) accumulation, whereas it activated phenolic acid biosynthesis and the jasmonate acid (JA) signaling pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed that SmMYB52 suppressed the transcription levels of key enzyme-encoding genes involved in the IAA biosynthetic pathway and activated key enzyme-encoding genes involved in the JA and phenolic acid biosynthesis pathways. In addition, yeast one-hybrid (Y1H) and dual-luciferase assay showed that SmMYB52 directly binds to and activates the promoters of several key enzyme genes for SalB biosynthesis, including SmTAT1, Sm4CL9, SmC4H1, and SmHPPR1, to promote the accumulation of SalB. This is the first report of a regulator that simultaneously affects root growth and the production of phenolic acids in S. miltiorrhiza.


Assuntos
Benzofuranos/metabolismo , Regulação da Expressão Gênica de Plantas , Salvia miltiorrhiza/metabolismo , Fatores de Transcrição/metabolismo , Ciclopentanos/metabolismo , Ácidos Indolacéticos/metabolismo , Oxilipinas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Salvia miltiorrhiza/crescimento & desenvolvimento
2.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4683-4688, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581076

RESUMO

China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.


Assuntos
Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Animais , China , Raízes de Plantas , Rizoma , Suínos
3.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3712-3721, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402296

RESUMO

This study aimed to analyze the methodological quality of systematic reviews of Shuxuening Injection and evaluate the efficacy and adverse reactions of Shuxuening Injection in the treatment of different diseases,in order to provide supportive evidence for clinical practice. Three Chinese databases and three English databases were retrieved to identify systematic reviews and Meta-analysis on the efficacy and safety of Shuxuening Injection in the treatment of diseases. The AMSTAR 2( a measurement tool to assess systematic reviews 2) tool was used to evaluate the methodological quality of the included systematic reviews,and tables were created to present the results of Meta-analyses. Twenty-four systematic reviews were included,all with very low methodological quality. Among the 16 AMSTAR-2 items,only 5 items had a compliance rate greater than 60. 0%,and 8 items had a compliance rate less than 50. 0%. For patients with cerebral infarction,Shuxuening Injection combined with conventional treatment was more effective than conventional treatment alone in terms of clinical efficiency and neurological deficit improvement. For patients with angina pectoris,Shuxuening Injection was superior to Danshen/Compound Danshen Injection in terms of the total effective rate of angina pectoris and total effective rate of ECG. The efficacy of Shuxuening Injection combined with conventional treatment is significantly better than conventional treatment.Shuxuening Injection( alone or combined with conventional treatments) was better than conventional treatments for cerebral hemorrhage,ischemic cerebrovascular disease,chronic pulmonary heart disease,vertigo and sudden deafness. Shuxuening Injection had better efficacy and lower incidence of adverse reactions,but the methodological quality of included systematic reviews was low. The results of this study still need to be verified by high-quality systematic reviews.


Assuntos
Salvia miltiorrhiza , Angina Pectoris/tratamento farmacológico , Medicamentos de Ervas Chinesas , Humanos , Injeções , Revisões Sistemáticas como Assunto
4.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360660

RESUMO

Salvia miltiorrhiza is a renowned model medicinal plant species for which 15 SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family genes have been identified; however, the specific functions of SmSPLs have not been well characterized as of yet. For this study, the expression patterns of SmSPL6 were determined through its responses to treatments of exogenous hormones, including indole acetic acid (IAA), gibberellic acid (GA3), methyl jasmonic acid (MeJA), and abscisic acid (ABA). To characterize its functionality, we obtained SmSPL6-ovexpressed transgenic S. miltiorrhiza plants and found that overexpressed SmSPL6 promoted the accumulation of phenolic acids and repressed the biosynthesis of anthocyanin. Meanwhile, the root lengths of the SmSPL6-overexpressed lines were significantly longer than the control; however, both the fresh weights and lateral root numbers decreased. Further investigations indicated that SmSPL6 regulated the biosynthesis of phenolic acid by directly binding to the promoter regions of the enzyme genes Sm4CL9 and SmCYP98A14 and activated their expression. We concluded that SmSPL6 regulates not only the biosynthesis of phenolic acids, but also the development of roots in S. miltiorrhiza.


Assuntos
Regulação da Expressão Gênica de Plantas , Hidroxibenzoatos/metabolismo , Organogênese Vegetal , Proteínas de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Salvia miltiorrhiza/crescimento & desenvolvimento , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Salvia miltiorrhiza/metabolismo
5.
Biomolecules ; 11(7)2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34356625

RESUMO

Monoamine oxidases (MAOs) and muscarinic acetylcholine receptors (mAChRs) are considered important therapeutic targets for Parkinson's disease (PD). Lipophilic tanshinones are major phytoconstituents in the dried roots of Salvia miltiorrhiza that have demonstrated neuroprotective effects against dopaminergic neurotoxins and the inhibition of MAO-A. Since MAO-B inhibition is considered an effective therapeutic strategy for PD, we tested the inhibitory activities of three abundant tanshinone congeners against recombinant human MAO (hMAO) isoenzymes through in vitro experiments. In our study, tanshinone I (1) exhibited the highest potency against hMAO-A, followed by tanshinone IIA and cryptotanshinone, with an IC50 less than 10 µM. They also suppressed hMAO-B activity, with an IC50 below 25 µM. Although tanshinones are known to inhibit hMAO-A, their enzyme inhibition mechanism and binding sites have yet to be investigated. Enzyme kinetics and molecular docking studies have revealed the mode of inhibition and interactions of tanshinones during enzyme inhibition. Proteochemometric modeling predicted mAChRs as possible pharmacological targets of 1, and in vitro functional assays confirmed the selective M4 antagonist nature of 1 (56.1% ± 2.40% inhibition of control agonist response at 100 µM). These findings indicate that 1 is a potential therapeutic molecule for managing the motor dysfunction and depression associated with PD.


Assuntos
Abietanos , Inibidores da Monoaminoxidase , Monoaminoxidase , Fenantrenos , Receptor Muscarínico M4 , Salvia miltiorrhiza/química , Abietanos/química , Abietanos/farmacologia , Animais , Células CHO , Cricetulus , Humanos , Monoaminoxidase/química , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Fenantrenos/química , Fenantrenos/farmacologia , Receptor Muscarínico M4/antagonistas & inibidores , Receptor Muscarínico M4/química , Receptor Muscarínico M4/genética , Receptor Muscarínico M4/metabolismo
6.
Phytochemistry ; 191: 112932, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34454170

RESUMO

The NAC (NAM, ATAF, and CUC) family members are specific transcription factors in plants. The large family is involved in many plant growth and developmental processes, as well as in abiotic/biotic stress responses. It has been well studied in the genomes of various plants, including Arabidopsis thaliana, tomato, and quinoa. However, identification and functional studies of NAC family members in medicinal Salvia miltiorrhiza are limited. Here, we systematically identified 84 NAC genes and named them according to their gene IDs in the recently sequenced genome. The phylogeny of NAC family protein sequences was analyzed using bioinformatics methods, which divided them into nine subfamilies. Then, their chromosomal locations, gene structures and conserved domains were analyzed comprehensively. To further investigate the regulatory functions of NACs in S. miltiorrhiza, we analyzed the response of 10 selected NAC genes to methyl jasmonate and used NAC2 for transgenic experiments. The overexpression of Sm-NAC2 decreased the tanshinone I and IIA contents by 56% and 62%, respectively. However, Sm-NAC2-RNAi promoted the accumulation of four tanshinones, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I, which increased 3.68-, 4.1-, 3.13- and 5.9- fold, respectively, compared with wild type. In the tanshinone biosynthetic pathways, the overexpression of Sm-NAC2 down-regulated CYP76AH1, and the silencing of Sm-NAC2 up-regulated the expression levels of HMGR1, DXS2, KSL2, and CYP76AH1. This study provides information on the evolution of Sm-NAC genes and their possible functions, and it lays a foundation for further research into the NAC family-associated regulation of tanshinone biosynthesis.


Assuntos
Salvia miltiorrhiza , Abietanos , Família , Regulação da Expressão Gênica de Plantas , Raízes de Plantas , Salvia miltiorrhiza/genética
7.
Phytochemistry ; 191: 112902, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34384921

RESUMO

Thirteen undescribed diterpenoid quinones were isolated from the dried roots of Salvia miltiorrhiza. Their structures were determined by extensive analysis, including NMR, HRESIMS, and IR. Their absolute configurations were determined by X-ray diffraction, calculated and experimental circular dichroism spectroscopy, and optical rotation. In the evaluation of bioactivities, salviadionether obviously inhibited the proliferation of HCT-116 cells. R-(+)-salmiltiorin E and R-(+)-grandifolia D both showed inhibitory activities on a variety of tumor cells. Salvianone ester A showed strong cytotoxicity to tumor-repopulating cells (TRCs) with an IC50 value of 2.19 µM.


Assuntos
Diterpenos , Salvia miltiorrhiza , Salvia , Diterpenos/farmacologia , Estrutura Molecular , Raízes de Plantas , Quinonas/farmacologia , Rizoma
8.
Sci Rep ; 11(1): 16210, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376708

RESUMO

With the increased incidence and recognition, ulcerative colitis (UC) has become a global public health problem in the world. Although many immunosuppressant and biological drugs have been used for UC treatment, the cure rate is still very low. It is necessary to find some safe and long-term used medicine for UC cure. Recently, the Chinese traditional herb Danshen has been investigated in the treatment of UC. However, it is a limitation of Danshen that many of the active components in Danshen are not easily absorbed by the human body. Probiotics could convert macromolecules into smaller molecules to facilitate absorption. Thus, Lactobacillus rhamnosus (F-B4-1) and Bacillus subtillis Natto (F-A7-1) were screened to ferment Danshen in this study. The fermented Danshen products were gavaged in the dextran sulfate sodium (DSS)-induced UC model mice. Danshen had better results to attenuate symptoms of DSS-induced UC after fermented with F-B4-1 and F-A7-1. Loss of body weight and disease activity index (DAI) were reduced. The abnormally short colon lengths and colonic damage were recovered. And fermented Danshen had the better inhibitory effect than Danshen itself on pro-inflammatory cytokine expression during DSS-induced UC. The results indicated that compared with Danshen, fermented Danshen relieved DSS-induced UC in mice more effectively. Danshen fermented by probiotics might be an effective treatment to UC in clinic stage in the future.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Salvia miltiorrhiza/química , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Citocinas/metabolismo , Feminino , Fermentação , Camundongos , Camundongos Endogâmicos C57BL
9.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2806-2815, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296579

RESUMO

The plant root-associated microbiomes include root microbiome and rhizosphere microbiome, which are closely related to plant life activities. Nearly 30% of photosynthesis products of plants are used to synthesize root compounds, there is evidence that root compounds regulate and significantly affect the root microbiome Tanshinones are the main hydrophobic components in Salvia miltiorrhiza. In order to study whether these compounds can regulate the root-associated microbiomes of S. miltiorrhiza, our study first identified a white root S. miltiorrhiza(BG) which contains little tanshinones. Retain of the fifth intron of tanshinones synthesis key enzyme gene SmCPS1 leading to the early termination of the SmCPS1 gene, and a stable white root phenotype. Further, wild type(WT) and BG were planted in greenhouse with nutrient soil(Pindstrup, Denmark) and Shandong soil(collected from the S. miltiorrhiza base in Weifang, Shandong), then high-throughput sequencing was used to analyze the root-associated microbiomes. The results showed that the tanshinones significantly affected the root-associated microbiomes of S. miltiorrhiza, and the impact on root microbiomes was more significant. There are significant differences between WT and BG root microbiomes in species richness, dominant strains and co-occurrence network. Tanshinones have a certain repelling effect on Bacilli which belongs to Gram-positive, while specifically attract some Gram-negative bacteria such as Betaproteobacteria and some specific genus of Alphaproteobacteria. This study determined the important role of tanshinones in regulating the structure of root-associated microbiomes from multiple angles, and shed a light for further improving the quality and yield of S. miltiorrhiza through microenvironment regulation.


Assuntos
Microbiota , Salvia miltiorrhiza , Abietanos , Raízes de Plantas
10.
Plant Sci ; 310: 110993, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34315580

RESUMO

Plant-specific SQUAMOSA promoter-binding protein-like (SPL) transcription factors play critical regulatory roles during plant growth and development. However, the functions of SPLs in Salvia miltiorrhiza (SmSPLs; a model medicinal plant) have not been reported. Here, the expression patterns and functions of SmSPL7 were characterized in S. miltiorrhiza. SmSPL7 was expressed in all parts of S. miltiorrhiza, with the highest expression level in the leaves, and could be inhibited by multiple hormones, including methyl jasmonate, auxin, abscisic acid, and gibberellin. SmSPL7 is localized within the nucleus and exhibits robust transcriptional activation activity. Transgenic lines overexpressing SmSPL7 demonstrated pronounced growth inhibition, accompanied by increased anthocyanin accumulation via the genetic activation of the anthocyanin biosynthesis pathway. However, SmSPL7 overexpression significantly decreased salvianolic acid B (SalB) production by inhibiting the transcripts of genes implicated in its biosynthesis pathway. Further analysis indicated that SmSPL7 directly binds to SmTAT1 and Sm4CL9 promoters and blocks their expression to inhibit the biosynthesis of SalB. Taken together, these results indicate that SmSPL7 is a negative regulator of SalB biosynthesis but positively regulates anthocyanin accumulation in S. miltiorrhiza. These findings provide new insights into the functionality of the SPL family while establishing an important foundation for further uncovering the crucial roles of SmSPL7 in the growth of S. miltiorrhiza.


Assuntos
Antocianinas/metabolismo , Hidroxibenzoatos/metabolismo , Proteínas de Plantas/metabolismo , Salvia miltiorrhiza/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/genética , Salvia miltiorrhiza/genética , Fatores de Transcrição/genética
11.
Int J Mol Sci ; 22(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299156

RESUMO

MicroRNAs (miRNAs) are important regulators of gene expression involved in plant development and abiotic stress responses. Recently, miRNAs have also been reported to be engaged in the regulation of secondary plant metabolism. However, there are few functional studies of miRNAs in medicinal plants. For this study, we obtained Sm-miR408 interference lines to investigate the function of Sm-miR408 in a medicinal model plant (Salvia miltiorrhiza). It was found that inhibiting the expression of Sm-miR408 could increase the content of salvianolic acid B and rosmarinic acid in the roots. The SmLAC3 and Sm-miR408 expression patterns were analyzed by qRT-PCR. A 5' RLM-RACE assay confirmed that Sm-miR408 targets and negatively regulates SmLAC3. Moreover, the overexpression of SmLAC3 in S. miltiorrhiza promoted the accumulation of salvianolic acids in the roots. Furthermore, the lignin content of the roots in overexpressed SmLAC3 lines was decreased. Taken together, these findings indicated that Sm-miR408 modulates the accumulation of phenolic acids in S. miltiorrhiza by targeting SmLAC3 expression levels.


Assuntos
Benzofuranos/metabolismo , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Salvia miltiorrhiza/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/crescimento & desenvolvimento
12.
Artigo em Inglês | MEDLINE | ID: mdl-34224965

RESUMO

The metabolomics approach based on the gas chromatography coupled to mass spectrometry (GC-MS) was adopted to explore the underlying mechanism of the anti-fatigue effect of Radix Salviae Miltiorrhizae (RSM), a famous herbal medicine in China used for multiple biological functions, in load-weighted swimming test in rat, combined with biochemical parameters evaluations. As a result, the metabolomics study followed by orthogonal partial least-square (OPLS) analysis could differentiate metabolic profiling between the control and exhaustive exercise group, showing the rats underwent an obvious metabolic perturbation, whereas RSM treatment restored scores plot close to normal and showed regulatory effects on the muscle metabolic profiles. The changed metabolic pathways of the potential biomarkers in response to the effect of RSM treatment for exhaustive exercise rats included in glucose metabolism (glucose, lactic acid, alanine), glutathione metabolism (glycine, glutamate, 5-oxo-proline), TCA cycle (succinic acid), arginine biosynthesis (glutamine, ornithine, urea), glyoxylate and dicarboxylate metabolism (serine, glycine), oxidative stress (taurine) and purine metabolism (inosine). In addition, intervention of RSM increased hepatic glycogen, muscle glycogen and serum glucose, and decreased triglyceride and blood urea nitrogen levels, indicating RSM treatment may regulate energy metabolism by increasing the rate of fat utilization, decrease the protein and carbohydrate utilization. Furthermore, RSM reduced exhaustive exercise-induced accumulation of the lipid peroxidation byproduct malonaldehyde and elevated antioxidants' levels, including reduced glutathione and superoxide dismutase, which might be a positive reflection of improved oxidant-antioxidant balance. Moreover, RSM could protect against exercise-induced muscle damage by attenuating creatine kinase release. In summary, RSM provided a good anti-fatigue effect by regulating energy metabolism, oxidant-antioxidant balance, and the endogenous metabolites in the exercising muscle. This study demonstrates that metabolomics is an effective tool for the estimation of the potential anti-fatigue effect of RSM and for the illustration of its pharmacological mechanism.


Assuntos
Medicamentos de Ervas Chinesas , Fadiga/metabolismo , Metaboloma/efeitos dos fármacos , Condicionamento Físico Animal/fisiologia , Salvia miltiorrhiza , Animais , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Ratos , Ratos Sprague-Dawley
13.
Front Public Health ; 9: 664841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222174

RESUMO

Background: Coronary heart disease (CHD) is one of the most common diseases in clinical cardiovascular practice, mainly afflicting the middle-aged and elderly. It will greatly affect elderly quality of life, and even affect their psychological and physical health. At present, CHD is treated with western drugs alone, but this can produce drug dependency. In recent years, Traditional Chinese Medicine (TCM) combine western drugs has been used as a complementary and alternative therapy, and its effectiveness and safety have been proven, attracting the attention of numerous researchers. Objective: Our study aimed to compare the efficacy of Aspirin with Combined Compound Danshen Dropping Pills had a superior effect on the treatment of Hemorheology and Blood Lipids in Middle-aged and Elderly Patients with CHD. Determine the effectiveness and safety of Aspirin with Combined Compound Danshen Dropping Pills in the treatment of CHD, and obtain high quality clinical evidence. Methods: Based on the PRISMA Statement, inclusion and exclusion criteria were formulated. Randomized controlled trials (RCTs) on the Effects of Aspirin with Combined Compound Danshen Dropping Pills on Hemorheology and Blood Lipids in Middle-aged and Elderly Patients with CHD were found following a search of 4 mainstream medical databases. RCTs found to meet the study's requirement were included; data information was then extracted, and the quality assessed using the Cochrane bias risk assessment tool. Through RevMan software, Meta analysis was carried out for overall TC, TG, HDL-C, LDL-C hematocrit, high shear viscosity, low shear viscosity, plasma viscosity, PAGM, and TXB2 effective rate. The relative risk (RR) and 95% confidence interval (95% CI) were calculated; heterogeneity was tested and its source found; publication bias was assessed through the Egger and Begg tests, and by means of funnel plots. Result: 22 RCTs were found, involving 1,987 cases. The results of the Meta analysis showed that, compared to drug therapy alone, Aspirin with Combined Compound Danshen Dropping Pills had a superior effect on the treatment of Hemorheology and Blood Lipids in Middle-aged and Elderly Patients with CHD. The meta analysis results show the effects on TC [MD = -0.91, 95% CI (-1.09, -0.73)], on TG [MD = -0.94, 95% CI (-1.22, -0.66)], on HDL-C [MD = 0.40, 95% CI (0.27, 0.53)], on LDL-C [MD = -0.99, 95% CI (-1.24, -0.74)], on hematocrit [MD = -2.69, 95% CI (-3.73, -1.65)], on high shear blood viscosity [MD = -1.11, 95% CI (-2.18, -0.05)], on low shear viscosity [MD = -0.79, 95% CI (-0.89, -0.68)], on plasma viscosity [MD = -0.26, 95% CI (-0.52, 0.01)], on PAMG [MD = -10.75, 95% CI (-16.84, -4.67)], and on TXB2 [MD = -11.84, 95% CI (-14.75, -8.92)]. The source of heterogeneity might be related to the state of patient, efficacy of drugs in the control group and difference in judgment criteria for efficacy. The Egger test and Begg test showed that publication bias did not occur in our study. Conclusions: The combination of compound dropping pill DSP with aspirin has some therapeutic effect on blood lipids and hemorheology in patients with CHD, ince some of the RCTs featured a very small sample size, the reliability and validity of our study's conclusion may have been affected as well; therefore, the explanation should be treated with some caution. In the future, a large number of higher-quality RCTs are still needed to confirm the results of our study.


Assuntos
Doença das Coronárias , Salvia miltiorrhiza , Idoso , Aspirina , Doença das Coronárias/tratamento farmacológico , Hemorreologia , Humanos , Lipídeos , Pessoa de Meia-Idade
14.
Phytomedicine ; 89: 153620, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34218216

RESUMO

BACKGROUND: Xin-Ke-Shu (XKS), a commonly used traditional Chinese medicine, has been clinically proven to be effective for treatment of acute myocardial ischemia (AMI). Numerous studies underscore the important role of fatty acid metabolism in the pathogenesis of AMI. PURPOSE: This study examined the relationship between free fatty acids (FFAs) and AMI and the contributions of individual herbs found in XKS to provide a basis for the study of the compatible principle of XKS. METHODS: UFLC-MS/MS-based targeted metabolomics was performed to analyze the levels of 15 FFAs in the plasma and myocardium of isoproterenol (ISO)-induced AMI rats treated with XKS and the subtracted prescriptions of XKS. Electrocardiogram data, H&E staining, biochemical analysis and western blotting were assayed to illustrate the cardioprotection of XKS and its subtracted prescription in AMI. Correlation analysis was used to reveal the relationship between the levels of FFAs and overexpressed proteins/biochemical enzymes. RESULTS: We found aberrant fatty acid metabolism in AMI rats. In both plasma and myocardium, the concentrations of most of quantified FFAs were significantly altered, whereas the concentrations of stearic acid and behenic acid were similar between the control and AMI groups. Correlation analysis revealed that palmitic acid, oleic acid, linoleic acid and arachidonic acid were potentially the most relevant FFAs to inflammatory and apoptotic proteins and CK-MB. Moreover, XKS effectively alleviated pathological alterations, FFA metabolism abnormity, inflammation and apoptosis found in the myocardium of AMI rats. Notably, the removal of Salvia miltiorrhiza and Pueraria lobata from XKS resulted in markedly regulation loss of cardioprotection during AMI, especially mediation loss of FFA metabolism. The other three herbs of XKS also played a role in improving AMI. CONCLUSION: Fatty acid metabolism aberrance occurred during AMI. S. miltiorrhiza and P. lobata play vital roles in the anti-inflammatory and anti-apoptotic action partially by regulating FFA levels. Our findings revealed potential novel clinical FFAs for predicting AMI and extended the insights into the compatible principle of XKS in which S. miltiorrhiza and P. lobata can potently modulate FFA metabolism.


Assuntos
Medicamentos de Ervas Chinesas , Ácidos Graxos não Esterificados/metabolismo , Isquemia Miocárdica , Pueraria , Salvia miltiorrhiza , Animais , Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Pueraria/química , Ratos , Salvia miltiorrhiza/química , Espectrometria de Massas em Tandem
15.
Theranostics ; 11(14): 6891-6904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093860

RESUMO

Rationale: Tanshinone, a type of diterpenes derived from salvia miltiorrhiza, is a particularly promising herbal medicine compound for the treatment of cancers including acute myeloid leukemia (AML). However, the therapeutic function and the underlying mechanism of Tanshinone in AML are not clear, and the toxic effect of Tanshinone limits its clinical application. Methods: Our work utilizes human leukemia cell lines, zebrafish transgenics and xenograft models to study the cellular and molecular mechanisms of how Tanshinone affects normal and abnormal hematopoiesis. WISH, Sudan Black and O-Dianisidine Staining were used to determine the expression of hematopoietic genes on zebrafish embryos. RNA-seq analysis showed that differential expression genes and enrichment gene signature with Tan I treatment. The surface plasmon resonance (SPR) method was used with a BIAcore T200 (GE Healthcare) to measure the binding affinities of Tan I. In vitro methyltransferase assay was performed to verify Tan I inhibits the histone enzymatic activity of the PRC2 complex. ChIP-qPCR assay was used to determine the H3K27me3 level of EZH2 target genes. Results: We found that Tanshinone I (Tan I), one of the Tanshinones, can inhibit the proliferation of human leukemia cells in vitro and in the xenograft zebrafish model, as well as the normal and malignant definitive hematopoiesis in zebrafish. Mechanistic studies illustrate that Tan I regulates normal and malignant hematopoiesis through direct binding to EZH2, a well-known histone H3K27 methyltransferase, and inhibiting PRC2 enzymatic activity. Furthermore, we identified MMP9 and ABCG2 as two possible downstream genes of Tan I's effects on EZH2. Conclusions: Together, this study confirmed that Tan I is a novel EZH2 inhibitor and suggested MMP9 and ABCG2 as two potential therapeutic targets for myeloid malignant diseases.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Hematopoese/efeitos dos fármacos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Neoplasias/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Animais Geneticamente Modificados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Imunoprecipitação da Cromatina , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Hematopoese/genética , Histonas/metabolismo , Humanos , Leucemia/enzimologia , Leucemia/genética , Metaloproteinase 9 da Matriz/genética , Proteínas de Neoplasias/genética , Complexo Repressor Polycomb 2/metabolismo , Ligação Proteica , RNA-Seq , Salvia miltiorrhiza/química , Ressonância de Plasmônio de Superfície , Transcriptoma/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
16.
Food Chem ; 363: 130282, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34144425

RESUMO

Green extraction and separation of natural products is crucial for food industry, and has been widely concerned. Compared with hydrophilic natural products, the green extraction and separation of hydrophobic natural products is more challenging. In this work, a novel method which coupled the ultrasound-assisted extraction with high-speed countercurrent chromatography (HSCCC) separation based on hydrophobic deep eutectic solvent (DES) was proposed for hydrophobic compounds extraction and recovery. By using the developed method, the hydrophobic compounds in Rosmarinus officinalis leaves, Ginkgo biloba leaves and Salvia miltiorrhiza roots have been successfully extracted and recovered. The results indicated that hydrophobic DESs are more effective for extraction hydrophobic compounds than hydrophilic DESs and traditional solvents. And hydrophobic DESs can be used as HSCCC separation solvents to separate and recover hydrophobic compounds effectively. The infinite possibilities of DESs components and their combinations can provide inexhaustible selective space for hydrophobic compounds in the HSCCC separation process.


Assuntos
Produtos Biológicos , Rosmarinus , Salvia miltiorrhiza , Ginkgo biloba , Folhas de Planta , Solventes
17.
Sci Rep ; 11(1): 12217, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108553

RESUMO

The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA's pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.


Assuntos
Abietanos/farmacologia , Hidrolases Anidrido Ácido/antagonistas & inibidores , Apoptose , Neoplasias Colorretais/tratamento farmacológico , Hidrolases/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Salvia miltiorrhiza/química , Abietanos/química , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Células Tumorais Cultivadas
18.
Biochem Pharmacol ; 190: 114637, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34062127

RESUMO

Salvia miltiorrhiza (Danshen) is a well-known traditional Chinese medicine for treating various diseases, such as breast cancer. However, knowledge regarding its mechanisms is scant. Herein, the active ingredient dihydrotanshinone I (DHT) in Salvia miltiorrhiza extract (SME), which binds ERp57 was identified and verified by an enzymatic solid-phase method combined with LC-MS/MS. DHT potentially inhibited ERp57 activity and suppressed ERp57 expression at both the RNA and protein levels. Molecular docking simulation indicated that DHT could form a hydrogen bond with catalytic site of ERp57. Moreover, ERp57 overexpression decreased DHT-induced cytotoxicity in MDA-MB-231 cells. Thereafter, the signaling pathway downstream of ERp57 was investigated by Western blot analysis. The mechanistic study revealed that DHT treatment resulted in activation of endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and cellular apoptosis. In conclusion, our data implied that DHT targeted ERp57 for inhibition and induced ER stress and UPR activation, which in turn triggered breast cancer cell apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Furanos/farmacologia , Fenantrenos/farmacologia , Isomerases de Dissulfetos de Proteínas/metabolismo , Quinonas/farmacologia , Antineoplásicos Fitogênicos/química , Domínio Catalítico , Linhagem Celular Tumoral , Cromatografia Líquida , Feminino , Furanos/química , Humanos , Modelos Moleculares , Fenantrenos/química , Fitoterapia , Conformação Proteica , Isomerases de Dissulfetos de Proteínas/genética , Quinonas/química , Salvia miltiorrhiza/química , Espectrometria de Massas em Tandem
19.
Food Res Int ; 144: 110366, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34053559

RESUMO

Post-harvest processing is a leading cause of metabolic changes and quality loss in food products. An untargeted metabolomics approach based on UHPLC-QTOF-MS was conducted to explain metabolic changes during post-harvest processing of Salvia miltiorrhiza. A rapid identification method was established for comprehensive characterization of 56 phenolic acids and 45 tanshinones. Enzymatic browning was found to be the primary factor impacting the metabolic profile. A decreasing in free phenolic acids along with increasing in bound polyphenols was observed correlated with the deepening of browning degree. The various substructures of bound polyphenols were explored to interpret the composition of browning-associated products. It has also been found that the steaming process and control of the moisture content during slicing can effectively reduce the influence of enzymatic browning. This metabolomics study will contribute to select the optimal post-harvest processing methods for S. miltiorrhiza and provide information for post-harvest processing of similar products.


Assuntos
Salvia miltiorrhiza , Metaboloma , Metabolômica , Raízes de Plantas , Polifenóis
20.
BMC Genomics ; 22(1): 315, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933003

RESUMO

BACKGROUND: ATP-binding cassette (ABC) transporters have been found to play important roles in metabolic transport in plant cells, influencing subcellular compartmentalisation and tissue distribution of these metabolic compounds. Salvia miltiorrhiza Bunge, known as Danshen in traditional Chinese medicine, is a highly valued medicinal plant used to treat cardiovascular and cerebrovascular diseases. The dry roots and rhizomes of S. miltiorrhiza contain biologically active secondary metabolites of tanshinone and salvianolic acid. Given an assembled and annotated genome and a set of transcriptome data of S. miltiorrhiza, we analysed and identified the candidate genes that likely involved in the bioactive metabolite transportation of this medicinal plant, starting with the members of the ABC transporter family. RESULTS: A total of 114 genes encoding ABC transporters were identified in the genome of S. miltiorrhiza. All of these ABC genes were divided into eight subfamilies: 3ABCA, 31ABCB, 14ABCC, 2ABCD, 1ABCE, 7ABCF, 46ABCG, and 10 ABCI. Gene expression analysis revealed tissue-specific expression profiles of these ABC transporters. In particular, we found 18 highly expressed transporters in the roots of S. miltiorrhiza, which might be involved in transporting the bioactive compounds of this medicinal plant. We further investigated the co-expression profiling of these 18 genes with key enzyme genes involved in tanshinone and salvianolic acid biosynthetic pathways using quantitative reverse transcription polymerase chain reaction (RT-qPCR). From this RT-qPCR validation, we found that three ABC genes (SmABCG46, SmABCG40, and SmABCG4) and another gene (SmABCC1) co-expressed with the key biosynthetic enzymes of these two compounds, respectively, and thus might be involved in tanshinone and salvianolic acid transport in root cells. In addition, we predicted the biological functions of S. miltiorrhiza ABC transporters using phylogenetic relationships and analysis of the transcriptome to find biological functions. CONCLUSIONS: Here, we present the first systematic analysis of ABC transporters in S. miltiorrhiza and predict candidate transporters involved in bioactive compound transportation in this important medicinal plant. Using genome-wide identification, transcriptome profile analysis, and phylogenetic relationships, this research provides a new perspective on the critical functions of ABC transporters in S. miltiorrhiza.


Assuntos
Salvia miltiorrhiza , Transportadores de Cassetes de Ligação de ATP/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Filogenia , Raízes de Plantas/genética , Salvia miltiorrhiza/genética
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