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1.
Medicine (Baltimore) ; 100(6): e23843, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578512

RESUMO

BACKGROUND: Diabetes refers to any group of metabolic diseases characterized by high blood sugar and generally thought to be caused by insufficient production of insulin, impaired response to insulin. Globally, patients with type 2 diabetes account for more than 85% of the total diabetic patients, and due to factors, such as obesity, aging, environment and lifestyle, the incidence of diabetes is rising. Salvia miltiorrhiza (SM) is a medicine used to treat diabetes in China. In recent years, it has been reported that SM has the effect of improving type 2 diabetes. However, there is no systematic review of its efficacy and safety yet. Therefore, we propose a systematic review to evaluate the efficacy and safety of SM for T2D. METHODS: Six databases will be searched: China National Knowledge Infrastructure (CNKI), China Biological Medicine (CBM), China Scientific Journals Database (CSJD), Wanfang database, PubMed, and EMBASE. The information is searched from January 2010 to July 2020. Languages are limited to English and Chinese. The primary outcomes include 2 hour plasma glucose, fasting plasma glucose, hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting plasma insulin. The secondary outcomes include clinical efficacy and adverse events. RESULTS: This systematic review will evaluate the efficacy and safety of Salvia miltiorrhiza in the treatment of type 2 diabetes. CONCLUSION: This systematic review provides evidence as to whether Salvia miltiorrhiza is effective and safe for type 2 diabetes. ETHICS: Ethical approval is not necessary as this protocol is only for systematic review and does not involve in privacy data or an animal experiment. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020110046.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Salvia miltiorrhiza/química , China/epidemiologia , Gerenciamento de Dados , Diabetes Mellitus Tipo 2/epidemiologia , Jejum/sangue , Feminino , Glucose/análise , Hemoglobina A Glicada/análise , Homeostase/efeitos dos fármacos , Humanos , Incidência , Insulina/sangue , Masculino , Medicina Tradicional Chinesa/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
2.
Nat Commun ; 12(1): 685, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514704

RESUMO

Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.


Assuntos
Abietanos/biossíntese , Sistema Enzimático do Citocromo P-450/genética , Evolução Molecular , Proteínas de Plantas/genética , Salvia miltiorrhiza/enzimologia , Abietanos/química , Ciclização , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/química , Genes de Plantas/genética , Genoma de Planta , Família Multigênica/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Salvia miltiorrhiza/química , Salvia miltiorrhiza/genética
3.
J Chromatogr A ; 1637: 461826, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33387914

RESUMO

In this work, a smartphone-based device was constructed for thin-layer chromatography (TLC) detection and semi-quantitative analysis of the components of Salvia miltiorrhiza. The key construction and shooting parameters were investigated by the relative peak area and signal-to-noise ratio. The best conditions were as follows: shooting height, 17 cm; angle between the UV lamp and TLC plate, 58°; exposure compensation, 0~0.2 EV; and shutter speed under daylight and UV 365 nm, 1/50 s and 1/5 s, respectively. These ideal conditions could be replicated by smartphones from different brands with different versions of software. With good precision, repeatability and stability, the developed device was used for the semi-quantitative analysis of salvianolic acid B, rosmarinic acid, cryptotanshinone, tanshinone I, tanshinone IIA, and miltirone in the TLC analysis of 10 batches of S. miltiorrhiza. The results were compared with those obtained by a TLC densitometric scanner and two common types of image processing software, i.e., Gelanalyzer and ImageJ. Except for salvianolic acid B in the TLC densitometric scanner, all results were not significantly different among these methods, which suggested that smartphones might be a useful tool for the quality control of traditional Chinese medicines.


Assuntos
Cromatografia em Camada Delgada/métodos , Salvia miltiorrhiza/química , Smartphone , Abietanos/análise , Benzofuranos/análise , Cromatografia Líquida de Alta Pressão , Cinamatos/análise , Depsídeos/análise , Medicamentos de Ervas Chinesas/química , Fenantrenos/análise , Controle de Qualidade
4.
Phytomedicine ; 81: 153419, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33360345

RESUMO

BACKGROUND: Salvia Miltiorrhiza Depside Salt (SMDS) was extracted from Salvia miltiorrhiza with high-quality control of active principles. In 2005, China's FDA approved the use of SMDS for stable angina pectoris (SAP), but the evidence of SMDS combined with aspirin remains unclear. PURPOSE: The aim of this study was to assess the clinical effectiveness and safety of SMDS combined with aspirin in patients with SAP. METHODS: A multicenter, pragmatic, three-armed parallel group and an individually randomized controlled superiority trial was designed. Participants aged 35 to 75 years old with SAP were recruited from four "Class Ⅲ Grade A" hospitals in China. Participants who were randomized into the SMDS group were treated with SMDS by intravenous drip. Participants in the control group received aspirin enteric-coated tablets (aspirin). Participants who were randomly assigned to the combination group received SMDS combined with aspirin. All participants received standard care from clinicians, without any restrictions. The primary outcome measure was thromboelastography (TEG). Secondary outcome measures included symptom score of the Seattle Angina Questionnaire (SAQ), visual analogue scale (VAS) score of traditional Chinese medicine (TCM) symptoms, platelet aggregation measured by light transmittance aggregometry (LTA), and fasting blood glucose. Effectiveness evaluation data were collected at baseline and ten days after treatment. Researchers followed up with participants for one month after treatment to determine whether adverse events (AEs) or adverse drug reactions (ADRs) such as bleeding tendency occurred. All statistical calculations were carried out with R 3.5.3 statistical analysis software. RESULTS: A total of 135 participants completed follow-up data on the primary outcome after ten days of treatment. Participants in the SMDS combined aspirin group had the highest improvement rate of sensitivity in AA% [p < 0.001, 95% CI (0.00-0.00)], from 30.6% before treatment to 81.6% after treatment. Participants with drug resistance (AA% < 20%) in the SMDS combined with aspirin group also had the highest sensitivity rate [p < 0.001, 95% CI (0.00-0.00)] after treatment (accounting for 81.0% of the combination group and 60.7% of the sensitive participants). The improvement of TCM symptoms in participants treated with SMDS combined with aspirin was significantly better than that of the aspirin group [MD = 1.71, 95% CI (0.15-3.27), p = 0.032]. There were no significant differences in other indexes (R, TPI, MA, K, CI, α value) of TEG, SAQ, platelet aggregation and fasting blood glucose among the three groups. No bleeding tendency or ADRs occurred in all participants. CONCLUSION: SMDS combined with aspirin is a clinically effective and safe intervention to treat adults aged 35 and older with SAP. This trial shows that SMDS combined with aspirin can significantly improve the sensitivity rate of AA% in TEG and the VAS score of TCM symptoms. Further large samples and high-quality research are needed to determine if certain participants might benefit more from SMDS combined with aspirin. The study protocol was registered in the Clinical Trials USA registry (registration No. NCT02694848).


Assuntos
Angina Estável/tratamento farmacológico , Aspirina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Salvia miltiorrhiza/química , Idoso , Angina Estável/etiologia , Aspirina/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Creatinina/sangue , Depsídeos/uso terapêutico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboelastografia , Resultado do Tratamento
5.
Am J Chin Med ; 48(6): 1455-1473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32933312

RESUMO

Uric acid nephropathy (UAN) is caused by excessive uric acid, which results in the damage of renal tissue via urate crystals deposition in the kidneys. The roots and rhizomes of Salvia miltiorrhiza Bunge (S. miltiorrhiza) have been clinically used in many prescriptions to treat uric acid-induced renal damage. This study investigates the uricosuric and nephroprotective effects of the ethyl acetate extract of S. miltiorrhiza (EASM) and tanshinone IIA (a major component of S. miltiorrhiza, Tan-IIA) on UAN and explores the underlying molecular mechanism. Both EASM and Tan-IIA significantly decreased serum uric acid (SUA), serum creatinine (SCR), urine uric acid (UUA), and increased urine creatinine (UCR), and blood urea nitrogen (BUN) levels in experimental UAN mice. In adenine and potassium oxonate-induced mice, EASM and Tan-IIA treatment alleviated renal dysfunction and downregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Moreover, EASM treatment significantly prevented excessive reactive oxygen species (ROS) production in uric acid-induced HK-2 cells and suppressed the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). EASM also suppressed ROS-activated mitogen-activated protein kinases (MAPKs) in vivo and in vitro. These results suggest that both EASM and Tan-IIA demonstrated inhibitory effects on UAN through relieving NOX4-mediated oxidative stress and suppressing MAPK pathways activation.


Assuntos
Abietanos/farmacologia , Abietanos/uso terapêutico , Cálculos Renais/tratamento farmacológico , Cálculos Renais/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Salvia miltiorrhiza/química , Ácido Úrico/metabolismo , Abietanos/isolamento & purificação , Animais , Células Cultivadas , Cristalização , Modelos Animais de Doenças , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cálculos Renais/etiologia , Camundongos , Camundongos Endogâmicos , Extratos Vegetais/isolamento & purificação
6.
Food Chem ; 331: 127365, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32619909

RESUMO

Phenolic acids from Salvia miltiorrhiza have been widely used in nutritious, health-promoting products with an increasing demand. In the current study, two biosynthetic genes RAS (rosmarinic acid synthase) and CYP98A14 (a cytochrome P450-dependent monooxygenase) were successfully introduced into S. miltiorrhiza hairy roots. Overexpression of RAS and CYP98A14 resulted in higher content of phenolic acids (up to over 3-fold) in transgenic lines compared to the control. Meanwhile, DPPH results revealed that engineered S. miltiorrhiza hairy roots had stronger antioxidant activities than the control. In addition, phenolic acid crude extracts of the engineered hairy root lines overexpressing RAS or CYP98A14 showed improved antibacterial activities compared to the control lines. Our work exhibits a useful strategy for enhancement of phenolic acid production and bioactivities of S. miltiorrhiza hairy roots by genetic manipulation of RAS and CYP98A14, and also provides a new resource material to obtain active phenolic acids for food and healthy products.


Assuntos
Aciltransferases/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Hidroxibenzoatos/metabolismo , Raízes de Plantas/química , Salvia miltiorrhiza/genética , Aciltransferases/genética , Antibacterianos/química , Antibacterianos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Salmonella/efeitos dos fármacos , Salvia miltiorrhiza/química , Salvia miltiorrhiza/metabolismo
7.
J Pharmacol Sci ; 143(3): 165-175, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32387002

RESUMO

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.


Assuntos
Tetracloreto de Carbono/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/microbiologia , Fitoterapia , Salvia miltiorrhiza/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Camundongos Endogâmicos ICR , Triterpenos/isolamento & purificação
8.
Environ Toxicol ; 35(10): 1043-1049, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32415908

RESUMO

In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF-II-induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF-II analog Leu27IGF-II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF-II-induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF-II-induced cardiac hypertrophy. Moreover, the anti-Leu27IGF-II-IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.


Assuntos
Crescimento Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fator de Crescimento Insulin-Like II/análogos & derivados , Mioblastos Cardíacos/efeitos dos fármacos , Receptor IGF Tipo 2/metabolismo , Salvia miltiorrhiza/química , Animais , Calcineurina/metabolismo , Cardiomegalia/prevenção & controle , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/isolamento & purificação , Antagonistas do Receptor de Estrogênio/farmacologia , Fulvestranto/farmacologia , Fator de Crescimento Insulin-Like II/farmacologia , Mioblastos Cardíacos/metabolismo , Mioblastos Cardíacos/patologia , Transporte Proteico , Ratos , Receptores Estrogênicos/metabolismo , Transdução de Sinais
9.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1090-1096, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237451

RESUMO

There were significant differences in phenolic acid content between fresh and dried Salvia miltiorrhiza before and after drying. That is to say, the content of phenolic acid in S. miltiorrhiza significantly increased with the increase of dehydration during the drying process.In order to investigate the differences and transformation of free and bound phenolic acids before and after the drying process of S.miltiorrhiza, we studied hydrolysis method, hydrolysates and hydrolysis regularity of phenolic acids in S.miltiorrhiza. UPLC method was used to determine four main hydrolysates of bound phenolic acids, namely danshensu, caffeic acid dimer(SMND-309), caffeic acid, przewalskinic acid A(prolithosperic acid), and three main free phenolic acids in S.miltiorrhiza, namely rosmarinic acid, lithospermic acid, salvianolic acid B. The results of the acid-base hydrolysis experiment of salvianolic acid showed that the alkaline hydrolysis effect was significantly better than acid hydrolysis. The optimal alkaline hydrolysis condition was hydrolysis at 70 ℃ for 4 h with 2 mol·L~(-1) NaOH solution containing 1% ascorbic acid(Vit C). The hydrolysates of free phenolic acids were the same with the hydrolysates of bound phenolic acids. Fresh S.miltiorrhiza contains a low level of free phenolic acids and a high level of bound phenolic acids, which were exactly opposite to dried S.miltiorrhiza. It was suggested that a large amount of bound phenolic acids was accumulated during the growth of S.miltiorrhiza. These bound phenolic acids were coupled with polysaccharides on the cytoderm through ester bonds to form insoluble phenolic acids, which was not easy to be detected by conventional methods. However, during drying and dehydration processes, the bound phenolic acids were converted to a large amount of free phenolic acids under the action of the relevant enzyme.


Assuntos
Dessecação , Hidroxibenzoatos/análise , Salvia miltiorrhiza/química
10.
Zhongguo Zhong Yao Za Zhi ; 45(3): 548-554, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237512

RESUMO

Study the suitability of organic film for salvianolic acid in the ultrafiltration process of Danshen Dizhuye. UPLC was used to analyze the migration of nine phenolic active ingredients in Danshen Dizhuye during ultrafiltration of PES hollow fiber membrane and PS hollow fiber membrane. The structural composition of multi-components was analyzed by three different batches of Danshen Dizhuye before and after ultrafiltration of the two membranes. The results showed that 9 phenolic active ingredients in Danshen Dizhuye did not change significantly after ultrafiltration through PES membrane. However, after ultrafiltration through PS membrane, the content of sodium danshensu, protocatechualdehyde, caffeic acid, 3-hydroxy-4-methoxycinnamic acid and rosmarinic acid in Danshen Dizhuye did not change significantly, while salvianolic acid D, salvianolic acid B and lithospermic acid decreased by about 20%, and the content of salvianolic acid A decreased significantly. The final content in equilibrium was only about 20% of the original solution. Therefore, an in-depth study on the migration particularity of salvianolic acid A in ultrafiltration membrane was the focuse. The results showed that the loss of salvianolic acid A was caused by both membranes during ultrafiltration, and salvianolic acid A was lost more in PS membrane. When the membrane was washed and regenerated, it was found that salvianolic acid A was detected in the ethanol washing solution, but not in the washing liquid, indicating that the loss of salvianolic acid A during the ultrafiltration was mainly adsorptive action. The results suggested that the migration of phenolic active ingredients in Danshen Dizhuye during the membrane ultrafiltration process did not completely follow the molecular weight passing rule of the membrane pore size. At the same time, it may be affected by factors, such as the structure of the membrane material, and the interaction between the membrane structure and the structure of components, and exhibit different migration behaviors during the ultrafiltration of the membrane.


Assuntos
Alcenos/química , Medicamentos de Ervas Chinesas/química , Polifenóis/química , Salvia miltiorrhiza/química , Ultrafiltração , Cromatografia Líquida de Alta Pressão
11.
Phytother Res ; 34(7): 1704-1720, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32185841

RESUMO

Microcirculation, which connects macrocirculation and cells between arterioles and venules, plays a major role in the early onset of a variety of diseases. In this article, a dextran-induced microcirculation dysfunction (MCDF) model rats were adopted to evaluate the effects and mechanism of Salvia miltiorrhiza stem-leaf extracts based on plasma and urine metabonomics. The results showed the effective components of S. miltiorrhiza stem-leaf could significantly improve the hemorheology and coagulation index of MCDF rats and callback the expression of endothelin-1 (ET-1), induciblenitric oxide synthase (iNOS), vascularendothelial growth factor (VEGF), P-Selectin, thromboxane A2, 6-keto-PGF1α , TNF-α, and interleukin-1ß to control group in MCDF rats. The decrease of microvessel density (MVD) in lung and thymus caused by MCDF was upgraded by Salvia miltiorrhiza stem-leaf. Based on the plasma and urine metabolic data, 20 potential biomarkers were identified. These biomarkers are mainly related to linoleic acid metabolism, glutathione metabolism, pantothenate and coenzyme A biosynthesis, pentose and glucuronate interconversions, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, beta-alanine metabolism, and citrate cycle. The results indicated that the effective components of S. miltiorrhiza stem-leaf can improve the hemorheological disorder and vascular endothelial function. Meanwhile, the effective components can regulate potential biomarkers and correlated metabolic pathway, which can provide guidance for the research and development of new drugs for MCDF.


Assuntos
Alcenos/química , Células Endoteliais/efeitos dos fármacos , Flavonoides/química , Hemorreologia/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Folhas de Planta/química , Caules de Planta/química , Polifenóis/química , Salvia miltiorrhiza/química , Animais , Masculino , Ratos , Ratos Wistar
12.
Pharm Biol ; 58(1): 219-224, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32202179

RESUMO

Context: Salvia miltiorrhiza Bge. (Labiatae) (SMB) is applied clinically for management of diabetic osteoporosis in China, and research results has suggested its potential action on renin-angiotensin system (RAS).Objective: This study screens and explores naturally occurring bioactive constituents from the root of SMB acting on renin activity and evaluates its osteoprotective efficacy in diabetic mice.Materials and methods: Human embryonic kidney (HEK) 293 cells, engineered to express human renin, were used as an in vitro model to identify bioactive compound, tanshinone IIA, inhibiting renin activity. The C57BL/6 mice (n = 10 in each group) with diabetes induced by streptozotocin (STZ) were intraperitoneally injected with tanshinone IIA (10 and 30 mg/kg). The mice without STZ treatment and the diabetic mice treated with aliskiren were used as non-diabetic control and positive control, respectively.Results: Tanshinone IIA was found to display inhibitory effects on renin activity of HEK-293 cells; moreover, it down-regulated protein expression of ANG II in human renin-expressed HEK-293 cells. Treatment of diabetic mice with tanshinone IIA with both doses could significantly decrease ANG II level in serum (from 16.56 ± 1.70 to 10.86 ± 0.68 and 9.14 ± 1.31 pg/mL) and reduce ANG II expression in bone, consequently improving trabecular bone mineral density and micro-structure of proximal tibial end and increasing trabecular bone area of distal femoral end in diabetic mice.Conclusions: This study revealed beneficial effects of tanshinone IIA on bone of diabetic mice, and potentially suggested the application of Salvia miltiorrhiza in the treatment of osteoporosis and drug development of tanshinone IIA as a renin inhibitor.


Assuntos
Abietanos/farmacologia , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/complicações , Osteoporose/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/metabolismo , Abietanos/isolamento & purificação , Angiotensina II/sangue , Animais , Anti-Inflamatórios/isolamento & purificação , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Osteoporose/etiologia , Osteoporose/metabolismo , Raízes de Plantas/química , Renina/genética , Salvia miltiorrhiza/química , Transfecção
13.
Ecotoxicol Environ Saf ; 192: 110311, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32061988

RESUMO

The uptake and accumulation of cadmium (Cd) in Salvia miltiorrhiza (Bge.) negatively affects the quality of its harvested roots, and seriously threatens human health. This study investigates the effect of a microbial inoculant (MI) and garbage enzyme (GE) on Cd uptake, the accumulation of bioactive compounds, and the community composition of microbes in the rhizosphere soil of S. miltiorrhiza under Cd stress. S. miltiorrhiza seedlings were transplanted to Cd-contaminated pots and irrigated with an MI, GE, a combination of an MI and GE (MIGE) or water (control). The results indicated that treatments with an MI, GE or MIGE can reduce Cd uptake in S. miltiorrhiza. The MIGE treatment had greater efficiency in reducing Cd uptake than the control (reduction by 37.90%), followed by the GE (25.31%) and MI (5.84%) treatments. Treatments with an MI, GE and MIGE had no significant impact on fresh and dry root biomass. Relative to the control, the MI treatment had the highest efficiency in increasing the accumulation of total tanshinones (an increase of 40.45%), followed by the GE treatment (40.08%), with the MIGE treatment (9.90%) treatment not having a more favorable effect than the separate application of an MI or GE. The salvianolic acid content for all groups was higher than the standard prescribed by Chinese pharmacopoeia, notwithstanding a slightly lower level in the treated groups relative to the control. In addition, metagenomic analysis indicated changes in the relative abundance of soil microbes associated with the bioremediation of heavy metals. The relative abundances of Brevundimonas, Microbacterium, Cupriavidus and Aspergillus were significantly greater in the treated groups than in the Control. These results suggest that using MI and GE, either separately or together, may not only improve the quality of S. miltiorrhiza but may also facilitate the microbial remediation of soil contaminated with Cd.


Assuntos
Cádmio/toxicidade , Salvia miltiorrhiza/efeitos dos fármacos , Salvia miltiorrhiza/metabolismo , Poluentes do Solo/toxicidade , Abietanos/metabolismo , Alcenos/análise , Biodegradação Ambiental , Biomassa , Cádmio/farmacocinética , Raízes de Plantas/efeitos dos fármacos , Polifenóis/análise , Rizosfera , Salvia miltiorrhiza/química , Microbiologia do Solo
14.
Adv Pharmacol ; 87: 1-41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089230

RESUMO

Danshen, the dried root of Salvia miltiorrhiza Bge, is a common medicinal herb in Traditional Chinese Medicine, which has been used for the treatment of a number of diseases for thousands of years. More than 2000 years ago, the Chinese early pharmacy monograph "Shennong Materia Medica" recorded that Danshen could be used for the treatment of gastrointestinal diseases, cardiovascular diseases, certain gynecological diseases, etc. Since then, Danshen has been widely used clinically in many different prescriptions for many different diseases, especially for the treatment of cardiovascular diseases. Nowadays, many pharmacological studies about the water-soluble components from Danshen have been reported, especially salvianolic acids. It turned out that salvianolic acids showed strong anti-lipid peroxidation and anti-thrombic activities, and among them, SalAA and SalAB were the most potent. This review focused on the achievements in research of salvianolic acids regarding their bioactivities and pharmacological effects. These studies not only shed light on the water-soluble active components of Danshen and their mechanisms at the molecular level, but also provided theoretical information for the development of new medicines from Danshen for the treatment of cardiovascular and cerebrovascular diseases, inflammatory diseases, metabolic diseases, etc.


Assuntos
Alcenos/análise , Alcenos/farmacologia , Medicamentos de Ervas Chinesas/química , Polifenóis/isolamento & purificação , Alcenos/química , Alcenos/farmacocinética , Animais , Apoptose/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa , Polifenóis/análise , Polifenóis/química , Polifenóis/farmacocinética , Polifenóis/farmacologia , Salvia miltiorrhiza/química
15.
Adv Pharmacol ; 87: 43-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089238

RESUMO

Danshen (Cai, et al. 2016) is the dry root and rhizome of the herbaceous plant Salvia miltiorrhiza Bge. of family labiatae, a perennial plant that is native to China and Japan. The primary modern clinical applications of Danshen are for heart disease, chronic hepatitis, early cirrhosis, cerebral ischemia and pulmonary heart disease. Emerging evidence from cellular, animal, and clinical studies has begun to illuminate the pharmacological attributes of the primary lipophilic tanshinones from Danshen, which include tanshinone I, tanshinone II, cryptotanshinone and dihydrotanshinone, etc. Tanshinones offer the properties of anti-oxidation, anti-inflammation, antitumor, phytoestrogenic activity, vasodilation, neuroprotection, regulate metabolic function and other pharmacological advances. This chapter will review the discovery of the pharmacodynamic mechanism and pharmacokinetic studies of tanshinones and Danshen for further clinical applications.


Assuntos
Abietanos/farmacologia , Produtos Biológicos/farmacologia , Salvia miltiorrhiza/química , Abietanos/química , Abietanos/farmacocinética , Animais , Apoptose/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neuroproteção/efeitos dos fármacos
16.
BMC Complement Med Ther ; 20(1): 28, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32020855

RESUMO

BACKGROUND: The tanshinones and phenolic acids in Salvia miltiorrhiza (also named Danshen) have been confirmed for the treatment of coronary heart disease (CHD), but the action mechanisms remain elusive. METHODS: In the current study, the co-expression protein interaction network (Ce-PIN) was used to illustrate the differences between the tanshinones and phenolic acids of Danshen in the treatment of CHD. By integrating the gene expression profile data and protein-protein interactions (PPIs) data, the Ce-PINs of tanshinones and phenolic acids were constructed. Then, the Ce-PINs were analyzed by gene ontology enrichment analyzed based on the optimal algorithm. RESULTS: It turned out that Danshen is able to treat CHD by regulating the blood circulation, immune response and lipid metabolism. However, phenolic acids may regulate the blood circulation by Extracellular calcium-sensing receptor (CaSR), Endothelin-1 receptor (EDNRA), Endothelin-1 receptor (EDNRB), Kininogen-1 (KNG1), tanshinones may regulate the blood circulation by Guanylate cyclase soluble subunit alpha-1 (GUCY1A3) and Guanylate cyclase soluble subunit beta-1 (GUCY1B3). In addition, both the phenolic acids and tanshinones may regulate the immune response or inflammation by T-cell surface glycoprotein CD4 (CD4), Receptor-type tyrosine-protein phosphatase C (PTPRC). CONCLUSION: Through the same targets of the same biological process and different targets of the same biological process, the tanshinones and phenolic acids synergistically treat coronary heart disease.


Assuntos
Abietanos/farmacologia , Doença das Coronárias/tratamento farmacológico , Hidroxibenzoatos/farmacologia , Mapas de Interação de Proteínas , Humanos , Salvia miltiorrhiza/química
17.
Food Chem ; 315: 126270, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32028199

RESUMO

An electrochemistry coupled to online quadrupole time-of-flight tandem mass spectrometry (EC/Q-TOF/MS) was applied to investigate the oxidative transformation and metabolic pathway of five phenolic acids in Danshen sample. Simulation of the phase I oxidative metabolism was carried out in an electrochemical reactor equipped with a glassy carbon working electrode. The phase II reactivity of the generated oxidative products towards biomolecules (such as glutathione) was investigated by ways of covalent adduct formation experiments. The results obtained by EC/MS were compared with well-known in vitro studies by conducting rat liver microsome incubations. Structures of the electrochemically produced metabolites were identified by accurate mass measurement and previously results in vivo metabolites. It was indicated that the electrochemical oxidation was in good accordance with similar products found in vivo experiments. In conclusion, this work confirmed that EC/Q-TOF/MS was a promising analytical tool in the prediction of metabolic transformations of functional foods.


Assuntos
Técnicas Eletroquímicas/métodos , Hidroxibenzoatos/farmacocinética , Salvia miltiorrhiza/química , Espectrometria de Massas em Tandem/métodos , Animais , Eletrodos , Glutationa/metabolismo , Hidroxibenzoatos/análise , Hidroxibenzoatos/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , Oxirredução , Ratos Sprague-Dawley
18.
Sci Rep ; 10(1): 3538, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103121

RESUMO

Instructions for Salvia miltiorrhiza polyphenol injections indicate abnormal liver function as an occasional adverse reaction, but the incidence of this adverse drug reaction (ADR) has increased in recent years. We assessed S. miltiorrhiza polyphenol ADRs by performing a nested case-control study(NCCS) and meta-analysis. In the NCCS, 2633 patients receiving this treatment in the First Affiliated Hospital of Bengbu Medical College were enrolled. Logistic regression models found that in 58 (2.2%) patients experiencing abnormal liver function, the risk for liver dysfunction was associated with sulfa drug allergy (OR = 7.874, 95%CI (1.280, 48.447), P = 0.026), payment methods (OR = 0.106, 95%CI (0.012, 0.934), P = 0.043), duration of administration (OR = 0.922, 95%CI (0.862, 0.986), P = 0.017), cefathiamidine (OR = 0.441, 95%CI (0.216, 0.900), P = 0.025), human serum albumin (OR = 1.958, 95%CI (1.011, 3.789), P = 0.046), Dazhu Rhodiola injection (OR = 2.599, 95%CI (1.112, 6.070), P = 0.027), or reduced glutathione (OR = 0.394, 95%CI (0.188, 0.826), P = 0.014). Meta-analysis of reports on S. miltiorrhiza polyphenol ADRs in controlled trials and other observational studies included 676 patients, of which 17 (2.17%; 95%CI (0.0105, 0.0358)) presented with liver dysfunction; associated ADR risk factors included co-administration of other drugs. Our NCCS and meta-analysis had similar ADR incidence rates, which were higher than the rate in the drug instructions. This study provides guidance for assessing liver dysfunction risks associated with S. miltiorrhiza polyphenol injections.


Assuntos
Monitoramento de Medicamentos , Fígado/metabolismo , Polifenóis , Salvia miltiorrhiza/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polifenóis/administração & dosagem , Polifenóis/efeitos adversos , Polifenóis/química , Polifenóis/farmacocinética
19.
AAPS PharmSciTech ; 21(2): 38, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897797

RESUMO

In the study, we developed a novel oral dosage form of Compound Danshen to resolve the problems of low bioavailability, disequilibrium in drug release, and stomach degradation of active components of Compound Danshen in conventional formulas. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was prepared using a semipermeable shell with the core components. Using a single-factor method, we obtained the optimal formulation that consisted of Salvia miltiorrhiza extract, Panax notoginseng extract, Borneol, sodium chloride, polyethylene oxide wsr-N10, hydroxypropyl-ß-cyclodextrin, and ludipress. Moreover, in vitro dissolution test showed simultaneous releases of active ingredients from Compound Danshen COPC over 12 h at pH 7.8, displaying zero-order release characteristics. The impetus of drug release mainly depended on the difference in osmotic pressure across the capsule shell. Next, scanning electron microscopy showed morphological changes in the capsule shell during the dissolution test. More importantly, pharmacokinetic study in beagle dogs indicated that relative bioavailability was 330.58% and retention time was greatly prolonged in Compound Danshen COPC, compared with those in marketed Compound Danshen tablet products. Finally, in vivo imaging studies in beagle dogs showed that COPC was stable in gastrointestinal tract and the drug was specifically released in the colon region. A colon-specific osmotic pump capsule (COPC) of Compound Danshen was developed and optimized to achieve simultaneous zero-order release of multiple active components of Compound Danshen in the colon. More importantly, the COPC have proved to improve the bioavailability and prolong the retention time of Compound Danshen, compared with those in a marketed product.


Assuntos
Formas de Dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Canfanos/química , Colo/metabolismo , Preparações de Ação Retardada , Cães , Composição de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Excipientes , Pressão Osmótica , Panax notoginseng/química , Salvia miltiorrhiza/química , Solubilidade
20.
Artigo em Inglês | MEDLINE | ID: mdl-31973978

RESUMO

In order to develop an affinity HPLC method for screening direct thrombin inhibitors from Traditional Chinese Medicine (TCM), thrombin was immobilized on the glutaraldehyde-modified amino silica gel and was used as thrombin stationary phase. A thrombin affinity column (TAC) was made by packing the thrombin stationary phase into a bare column (2.0 * 1.0 mm, i.d.). The direct thrombin inhibitors could be screened through this TAC column. For the purpose of improvement of the discovery efficiency, a TAC-HPLC-MS/MS system was used to screen thrombin inhibitors from Radix Salviae Miltiorrhiae (RSM), a famous traditional Chinese medicine. After optimization of all the conditions, cryptotanshinone (Cry), dihydrotanshinone I (Dih-I) and tanshinone IIA (Tan-IIA) were screened out and identified as potential active components. The anticoagulant effects of these three compounds were tested by anticoagulant experiments in vitro. Furthermore, the interaction of three compounds with thrombin was studied by molecular docking. The result shows they have the potential to be used as preventive drugs. In short, this method can be used to screen anticoagulant drugs from traditional Chinese medicine, which provides convenience for screening anticoagulant drugs.


Assuntos
Antitrombinas , Cromatografia de Afinidade , Medicamentos de Ervas Chinesas/química , Salvia miltiorrhiza/química , Trombina/metabolismo , Animais , Antitrombinas/análise , Antitrombinas/metabolismo , Testes de Coagulação Sanguínea , Cromatografia de Afinidade/instrumentação , Cromatografia de Afinidade/métodos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Simulação de Acoplamento Molecular , Coelhos , Espectrometria de Massas em Tandem/métodos , Trombina/química
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