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1.
J Agric Food Chem ; 68(7): 2054-2062, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31995984

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disease which is partly characterized by the aggregation of hyperphosphorylated Tau proteins forming neurofibrillary tangles that promote AD pathogenesis. In this study, we investigated the effects of tanshinone IIA (Tan IIA) isolated from Salvia miltiorrhiza on Tau degradation in the treatment of AD. The results showed that Tan IIA reduced the Tau expression and attenuated Tau phosphorylation in N2a cells, Tau-overexpressing cells, and 3×Tg-AD mouse primary neuron cells. Moreover, Tan IIA increased polyubiquitinated Tau accumulation and induced proteasomal degradation of the Tau protein. Additionally, Tan IIA became bound to the Tau protein and inhibited the formation of heparin-induced Tau fibrils. In summary, Tan IIA can increase polyubiquitinated Tau accumulation and induce the proteasomal degradation of the Tau protein and the binding of Tan IIA to the Tau protein, inhibiting the formation of Tau fibrils. Tan IIA may be further explored as a potential candidate for AD treatment.


Assuntos
/farmacologia , Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Salvia miltiorrhiza/química , Ubiquitinas/metabolismo , Proteínas tau/química , Proteínas tau/metabolismo , Doença de Alzheimer/genética , Animais , Linhagem Celular , Humanos , Camundongos , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Proteólise/efeitos dos fármacos , Proteínas tau/genética
2.
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 , 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
3.
Phytochemistry ; 169: 112183, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704239

RESUMO

Phenolic acids and tanshinones are the two groups of pharmaceutically active metabolites in Salvia miltiorrhiza Bunge. Their contents are the key quality indicator to evaluate S. miltiorrhiza. bHLH transcription factors have important roles in regulation of plant specialised metabolism. In this study, an endogenous bHLH transcription factor, SmbHLH3, was identified and functionally analyzed. SmbHLH3 was presented in all the six tissues and mostly expressed in fibrous roots and flowers. It was localized to the nucleus. Overexpression of SmbHLH3 decreased both phenolic acids and tanshinones contents. Contents of caffeic acid and rosmarinic acid were both decreased to 50% of the control. And accumulation of salvianolic acid B was decreased as much as 62%. Content of cryptotanshinone, dihydrotanshinone I, tanshinone I and tanshinone IIA in SmbHLH3-overexpression lines were reduced 97%, 62%, 86% and 91%, respectively. In the transgenic lines, expression of C4H1, TAT and HPPR in phenolic acids pathways were reduced to about 43%, 66% and 77% of the control, respectively. For tanshinone biosynthetic pathways, transcripts of DXS3, DXR, HMGR1, KSL1, CPS1 and CYP76AH1 were reduced to 46%, 65%, 78%, 57%, 27% and 62% of the control, respectively. There was an E/G-box specific binding site in SmbHLH3, which may bind the E/G-box present in promoter region of these biosynthetic pathway genes. Y1H results indicated that SmbHLH3 could bind the promoter of TAT, HPPR, KSL1 and CYP76AH1. These findings indicated that SmbHLH3 downregulate both phenolic acids and tanshinone accumulation through directly suppressing the transcription of key enzyme genes.


Assuntos
/metabolismo , Hidroxibenzoatos/metabolismo , Raízes de Plantas/metabolismo , Salvia miltiorrhiza/metabolismo , Fatores de Transcrição/metabolismo , /química , Regulação para Baixo , Hidroxibenzoatos/química , Estrutura Molecular , Raízes de Plantas/química , Salvia miltiorrhiza/química , Fatores de Transcrição/química , Fatores de Transcrição/genética
4.
Talanta ; 206: 120195, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514831

RESUMO

The ability to separate bioactive compounds from herbal medicines, which contain abundant components, is crucial for drug discovery. Conventional Countercurrent chromatography (CCC) methods for separating bioactive compounds are labor intensive and show low efficiency. Here, we present a novel integrative CCC method for separating lysine-specific demethylase 1 (LSD1) inhibitors from the roots of Salvia miltiorrhiza (RSM). The methanol extracts of RSM were separated into hydrosoluble and liposoluble fractions, which were online stored in coils. Subsequently, the targeting LSD1 constituents were isolated using isocratic, gradient, or recycling elution mode. All separation processes could be accomplished using one CCC apparatus. Using our separation strategy, two phenylpropanoids and four tanshinones were isolated, which were determined to be new classes of natural LSD1 inhibitors. Salvianolic acid B, which showed the most potent inhibitory activity with an IC50 of 0.11 µM, exhibiting a considerable potential as an anticancer agent. Promisingly, the integrative CCC could be a crucial tool for the target separation of enzyme inhibitors from herbal medicines.


Assuntos
Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Raízes de Plantas/química , Salvia miltiorrhiza/química , Benzofuranos/isolamento & purificação , Benzofuranos/metabolismo , Benzofuranos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cinamatos/isolamento & purificação , Cinamatos/metabolismo , Cinamatos/farmacologia , Distribuição Contracorrente/métodos , Depsídeos/isolamento & purificação , Depsídeos/metabolismo , Depsídeos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Histona Desmetilases/metabolismo , Humanos , Simulação de Acoplamento Molecular , Fenantrenos/isolamento & purificação , Fenantrenos/metabolismo , Fenantrenos/farmacologia , Ligação Proteica
5.
J Ethnopharmacol ; 247: 112284, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31604137

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb pair, the most fundamental and simplest form of herb compatibility, serves as the basic building block of traditional Chinese medicine formulae. The Danshen-Honghua herb pair (DH), composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen in Chinese) and Carthami Flos (Honghua in Chinese), has remarkable clinical efficacy to cure cardio-cerebrovascular diseases. This study was designed to investigate the pharmacodynamics of DH in comparison with single herbs and pharmacokinetics of DH relative to Danshen in acute myocardial ischemic injury. MATERIALS AND METHODS: Sixty male Wistar rats were divided into control, model and drug treated groups. The acute myocardial ischemia rat model was induced by administering 85 mg/kg/d isoproterenol (ISO) subcutaneously for two consecutive days. For pharmacodynamic study, histopathological and biochemical analysis were performed to assess the anti-myocardial ischemic effects. While for pharmacokinetic study, a UPLC-MS/MS method was developed for determination of nine main active ingredients, namely danshensu, protocatechuic acid, protocatechualdehyde, caffeic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and salvianolic acid C in rat plasma. RESULTS: The histopathological and biochemical analysis revealed that DH exerted enhanced anti-myocardial ischemic effects against the ISO-induced myocardial ischemia compared with single herbs. The pharmacokinetic study indicated that DH could significantly increase the t1/2z of danshensu, Tmax, AUC0-∞ and MRT0-t of protocatechuic acid in comparison with Danshen alone in normal rats, but more importantly elevate systemic exposure level and prolong t1/2z of protocatechualdehyde, caffeic acid, Tmax of danshensu in acute myocardial ischemia rats. CONCLUSIONS: Our findings demonstrated the greater effects of DH after the compatibility in ISO-induced acute myocardial ischemia rats at pharmacodynamic and pharmacokinetic levels and provided valuable information for clinical application of herb pairs.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Salvia miltiorrhiza/química , Administração Oral , Animais , Carthamus tinctorius , China , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Etnofarmacologia , Humanos , Isoproterenol/toxicidade , Masculino , Infarto do Miocárdio/induzido quimicamente , Ratos
6.
Phytomedicine ; 66: 153110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790900

RESUMO

BACKGROUND: The root of Salvia miltiorrhiza f. alba (RSMA) (Lamiaceae) is used for the treatment of patients with thromboangiitis obliterans (TAO) in traditional Chinese medicine. Previously, a mixture of phenolic acids extracted from RSMA has shown significant protective effects on TAO rats. PURPOSE: This study investigates the inhibitory effects of salvianolic acid B on TAO induced by sodium laurate injection in rats to explore the effective constituents of RSMA in TAO treatment. METHODS: TAO rats were developed using injected sodium laurate. After treatment with ligustrazine hydrochloride (15 mg/kg) and various doses of salvianolic acid B (10, 20, 40 mg/kg) by tail intravenous injection, levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and endothelin-1 (ET-1) in plasma were determined using enzyme-linked immunosorbent assay. The right femoral arteries were studied by hematoxylin and eosin staining and immunohistochemical analysis to determine pathological changes and overexpression of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in the femoral artery walls of TAO rats. RESULTS: Salvianolic acid B significantly decreased the expressions of TXB2 and ET-1 and increased the expression of 6-keto-PGF1α in plasma, and significantly inhibited the overexpression of TNF-α and iNOS in the femoral artery walls of TAO rats at medium and high doses. CONCLUSION: Salvianolic acid B has a protective effect on TAO rats. The mechanism may involve inhibition of thrombosis and TAO-associated inflammatory responses, which may explain the success of RSMA treatment of TAO in humans in traditional Chinese medical practice. Hence, it may be a potential drug for TAO treatment in conventional medicine.


Assuntos
Benzofuranos/farmacologia , Inflamação/prevenção & controle , Salvia miltiorrhiza/química , Tromboangiite Obliterante/tratamento farmacológico , Trombose/prevenção & controle , Animais , Benzofuranos/química , Humanos , Ácidos Láuricos/efeitos adversos , Masculino , Medicina Tradicional Chinesa , Raízes de Plantas/química , Ratos , Ratos Wistar , Tromboangiite Obliterante/induzido quimicamente
7.
J Agric Food Chem ; 67(44): 12199-12207, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31595753

RESUMO

Salvianolic acid A (Sal A) has a wide range of pharmacological activities. To date, there have been no systematic and detailed metabolite research data of Sal A after oral administration in vitro and in vivo. In this study, a rapid and systematic method based on ultrafast liquid chromatography-quadrupole-time-of-flight mass spectrometry was developed to detect metabolites of Sal A in vitro (human liver microsome, human intestinal microbiota, artificial gastric, and intestinal juice) and in vivo (urine, plasma, feces, and various organs collected after oral administration of Sal A to normal rats and pseudo-germ-free rats). A total of 26 metabolites of Sal A were characterized. These metabolites were formed through extensive metabolic reactions, such as hydroxylation, hydrogenation, and glucuronidation reactions. This study provides novel possibility for exploring the potential biological mechanism of Sal A, and aids the promotion of clinical application.


Assuntos
Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Lactatos/química , Lactatos/metabolismo , Espectrometria de Massas/métodos , Salvia miltiorrhiza/química , Adulto , Animais , Feminino , Humanos , Masculino , Metaboloma , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley , Adulto Jovem
8.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3724-3731, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602945

RESUMO

Testing and analysis of chemical markers is currently the prevailing approach for quality assessment of traditional Chinese medicines. However,several important issues remain to be addressed,including the trade-off between accuracy and coverage. In this study,in order to give full play to the advantages of their respective methods and provide technical support for more comprehensively and rapidly evaluate the quality of Danshen Injection products,a fingerprint method was coupled with quantitative analysis of multicomponents by single marker( QAMS),with Danshen Injection as the carrier. Ultra performance liquid chromatography( UPLC) was used to establish the quantitative fingerprint. The UPLC fingerprints contained 13 common peaks,11 of which were identified by using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS). Furthermore,with sodium danshensu as the internal reference substance,relative correction factors( RCFs) of protocatechuic aldehyde,caffeic acid,rosmarinic acid,lithospermic acid,and salvianolic acid B were calculated through slope analysis method,and the QAMS method was adopted to determine the contents of these 6 components. The UPLC fingerprint was employed to assess the consistency of 12 batches of Danshen Injection,which showed good batch-to-batch consistency with similarity higher than 0. 99. In the comparison of contents of the six constituents obtained by QAMS and external standard method( ESM),RSD was all less than 4. 3%,indicating the good accuracy of the QAMS method. The QAMS method developed in this study combined with UPLC fingerprint can comprehensively reflect the internal quality of Danshen Injection when only the reference substance sodium danshensu is consumed,with greatly reduced detection cost and time. It provides a technical basis for further improving the quality standard of Danshen Injection.


Assuntos
Medicamentos de Ervas Chinesas/normas , Salvia miltiorrhiza/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Injeções , Espectrometria de Massas , Controle de Qualidade
9.
Artif Cells Nanomed Biotechnol ; 47(1): 4030-4037, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31603005

RESUMO

Spinal cord injury (SCI) can lead to varying degrees of sensory and motor dysfunction. Salvianolic acid B (Sal-B) is the dominating bioactive constituent of Danshen, which has been reported to alleviate liver fibrosis and exert neuroprotective effects. But, the influence of Sal-B in SCI remains mysterious. The research planned to delve the protective function of Sal-B in hydrogen peroxide (H2O2)-caused PC-12 cell injury. H2O2-caused PC-12 cells injury model was built, CCK-8, Transwell and flow cytometry experiments were enforced to assess cell proliferation, migration and apoptosis. The microRNA (miR)-26a plasmid and the matching control were transfected into PC-12 cells, subsequently, the influence of miR-26a inhibition in H2O2-corrupted PC-12 cells was evaluated. The cell growth-correlated factors and PI3K/AKT and MEK/ERK pathways were assayed through western blot assay. Results corroborated that Sal-B eased H2O2-evoked injury in PC-12 cells. Ascended miR-26a was monitored in Sal-B and H2O2-exposed cells. MiR-26a inhibition annulled the protective action of Sal-B in H2O2-corrupted cells. The protective function of Sal-B was enabled through activating PI3K/AKT and MEK/ERK pathways. These findings delineated that Sal-B protected PC-12 cells against H2O2-caused injury through ascending miR-26a via initiating PI3K/AKT and MEK/ERK pathways. Highlights H2O2 causes PC-12 cell injury; Sal-B eases H2O2-caused PC-12 cell injury; Sal-B protects PC-12 cells against H2O2-caused injury via elevating miR-26a; Sal-B activates AKT and MEK/ERK pathways via modulating miR-26a.


Assuntos
Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , MicroRNAs/genética , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos
10.
Complement Ther Med ; 46: 87-94, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519293

RESUMO

BACKGROUND: caffeine is a major constituent in numerous foods, beverages, dietary supplements and medications.Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav, and Salvia miltiorrhiza Bunge are traditional medicines commonly used in Asia. OBJECTIVES: to compare the pharmacokinetics of caffeine in humans before and after consuming an aqueous extract of A. dahurica or S. miltiorrhiza, and to propose a mechanistic explanation for in vivo caffeine metabolism inhibition based on in vitro data obtained with human liver microsomes. METHODS: Each of the four human volunteers was given a single oral dose of caffeine before and after consuming an A. dahurica or S. miltiorrhiza extract. Saliva samples were collected from the volunteers at pre-determined time points after receiving caffeine. The saliva samples were analyzed for unchanged caffeine using liquid chromatography. RESULTS: A. dahurica and S. miltiorrhiza extracts were capable of inhibiting caffeine metabolism in the human volunteers. In a separate study, cytochrome (CYP) 1A2-mediated caffeine demethylase activity was studied in incubation containing human liver microsomes, ß-nicotinamide adenine dinucleotide phosphate, and an herbal extract (or a pure bioactive chemical from the herbs). In all cases, CYP1A2 activity was decreased with an increasing inhibitor concentration, confirming the inhibition of caffeine metabolism in vivo. Caffeine metabolism inhibition most likely involved the competitive and/or non-competitive mechanism. CONCLUSION: Because a high level of caffeine in the plasma may result in adverse health effects in humans, care must be exercised when caffeine is consumed together with A. dahurica or S. miltiorrhiza.


Assuntos
Angelica/química , Cafeína/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacocinética , Salvia miltiorrhiza/química , Adulto , Citocromo P-450 CYP1A2/metabolismo , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Masculino , Extratos Vegetais/química , Adulto Jovem
11.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510010

RESUMO

Prostate cancer (PCa), an epithelial malignant tumor, is the second common cause of cancer death among males in western countries. Thus, the development of new strategies is urgently needed. Tanshinones isolated from Salvia miltiorrhiza and its synthetic analogs show various biological activities including anticancer effects. Among them, the tanshinone analog 2-((Glycine methyl ester)methyl)-naphtho (TC7) is the most effective, with better selectivity and lower toxicity. Therefore, in this work, the effect of TC7 against PCa was investigated through assessing the molecular mechanisms regulating the growth, metastasis, and invasion of PCa cells. Human PCa cells, PC3 and LNCAP, were used to evaluate TC7 mechanisms of action in vitro, while male BALB/c nude mice were used for in vivo experiments by subjecting each mouse to a subcutaneous injection of PC3 cells into the right flank to evaluate TC7 effects on tumor volume. Our in vitro results showed that TC7 inhibited cell proliferation by arresting the cell cycle at G2/M through the regulation of cyclin b1, p53, GADD45A, PLK1, and CDC2/cyclin b1. In addition, TC7 induced cell apoptosis by regulating apoptosis-associated genes such as p53, ERK1, BAX, p38, BCL-2, caspase-8, cleaved-caspase-8, PARP1, and the phosphorylation level of ERK1 and p38. Furthermore, it decreased DNA synthesis and inhibited the migration and invasion ability by regulating VEGF-1 and MMP-9 protein expression. Our in vivo evidence supports the conclusion that TC7 could be considered as a potential promising chemotherapeutic candidate in the treatment of PCa.


Assuntos
/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Neoplasias da Próstata/prevenção & controle , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , /química , Animais , Antineoplásicos Fitogênicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Fitoterapia/métodos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Salvia miltiorrhiza/química
12.
Fitoterapia ; 137: 104285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386897

RESUMO

Botanical-based natural products are an important resource for medicinal drug discovery and continue to provide diverse pharmacophores with therapeutic potential against cancer and other human diseases. A prototype Traditional Chinese Medicine (TCM) plant extract library has been established at the US National Cancer Institute, which contains both the organic and aqueous extracts of 132 authenticated medicinal plant species that collectively represent the potential therapeutic contents of most commonly used TCM herbal prescriptions. This library is publicly available in 96- and 384- well plates for high throughput screening across a broad array of biological targets, as well as in larger quantities for isolation of active chemical ingredients. Herein, we present the methodology used to generate the library and the preliminary assessment of the anti-proliferative activity of this crude extract library in NCI-60 human cancer cell lines screen. Particularly, we report the chemical profiling and metabolome comparison analysis of four commonly used TCM plants, namely Brucea javanica, Dioscorea nipponica, Cynanchum atratum, and Salvia miltiorrhiza. Bioassay-guided isolation resulted in the identification of the active compounds, and different extraction methods were compared for their abilities to extract cytotoxic compounds and to concentrate biologically active natural products.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/isolamento & purificação , Brucea/química , Linhagem Celular Tumoral , China , Cynanchum/química , Dioscorea/química , Descoberta de Drogas , Humanos , Medicina Tradicional Chinesa , National Cancer Institute (U.S.) , Compostos Fitoquímicos/isolamento & purificação , Salvia miltiorrhiza/química , Estados Unidos
13.
Chem Biodivers ; 16(9): e1900364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381262

RESUMO

Two new C13 -polyketides, aureonitols A and B (1 and 2), along with five known compounds (3-7), were isolated from the solid fermentation culture of the plant endophytic fungus Chaetomium globosum from the aerial parts of Salvia miltiorrhiza. The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic data analysis and computed methods. Compound 5 was found to display the remarkable antimicrobial activities against four multidrug-resistant bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Staphylococcus epidermidis) with MIC values of 3.13-6.25 µg/mL (ciprofloxacin: 0.78-1.56 µg/mL), and also against all tested fungal strains with MIC values of 3.13-25 µg/mL (ketoconazole: 0.78-12.50 µg/mL).


Assuntos
Antibacterianos/farmacologia , Chaetomium/química , Salvia miltiorrhiza/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Chaetomium/metabolismo , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Fermentação , Testes de Sensibilidade Microbiana , Conformação Molecular , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
14.
Carbohydr Polym ; 223: 115125, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31426969

RESUMO

This study evaluates the chemical structure of a heteropolysaccharide (PSF-W-1) from the endophytic fungus Trichoderma atroviride and its effects on the production of tanshinones in Salvia miltiorrhiza hairy roots. The total carbohydrate content of isolated PSF-W-1 was determined to be 97.72%. PSF-W-1 has a relative molecular weight of 36.13 kDa and contains mannose, glucose and galactose in molar ratios of 1.00:4.86:2.25. Through methylation analysis, IR and NMR, PSF-W-1 was determined to possess a backbone of →4)-ß-D-Glcp-(1→6)-α-D-Galp-(1→4)-ß-D-Manp-(1→6)-α-D-Galp-(1→ with two side chains ß-D-Glcp-(1→4)-ß-D-Glcp-(1→ attached to O3 of 1,6-α-D-Galp. Bioactivity tests suggested that PSF-W-1 was responsible for boosting the S. miltiorrhiza hairy root growth and the biosynthesis of dihydrotanshinone I, tanshinone I, tanshinone IIA and cryptotanshinone in hairy roots. According to this study, PSF-W-1 might be utilized as a potent stimulator of tanshinones synthesis.


Assuntos
/biossíntese , Raízes de Plantas/química , Polissacarídeos/metabolismo , Salvia miltiorrhiza/química , Trichoderma/química , /química , Estrutura Molecular , Raízes de Plantas/metabolismo , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Salvia miltiorrhiza/metabolismo
15.
Artif Cells Nanomed Biotechnol ; 47(1): 2846-2854, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31299869

RESUMO

Biosynthesis of silver nanoparticles (AgNPs) from the medicinal plants has been considered as a remarkable approach of several therapeutic innovations and successful drug delivery. Silver nanoparticles were biosynthesized with Salvia miltiorrhiza, Chinese medicinal herb and assessed for its anticarcinogenic property. Synthesis of AgNPs was characterized by several studies such as UV-absorbance and it shows peak values in the range of 425-445 nm. The sizes of the nanoparticles are confirmed by dynamic light scattering analysis and it shows 100 nm. Furthermore, transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDX) was to confirm the shape and Ag particles are present in the synthesized materials. FTIR analysis to find out the active biomolecules located in the surface of the synthesized particles. This AgNPs from S. miltiorrhiza inhibits the growth of Bacillus subtillis, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumonia. Furthermore, the anticancer potential of AgNPs is examined in prostate adenocarcinoma (LNCaP) cell lines. In this study, we found the AgNPs effectively induces cytotoxicity, ROS and apoptosis by modulation of intrinsic apoptoic Bcl2, Bclxl, Bax and Caspase 3 protein expressions in LNCap cell lines. Based on the study, synthesis of AgNPs from S. miltiorrhiza shows eco-friendly and it exhibits antimicrobial and anticarcinogenic effects.


Assuntos
Nanopartículas Metálicas/química , Extratos Vegetais/química , Folhas de Planta/química , Neoplasias da Próstata/patologia , Salvia miltiorrhiza/química , Prata/química , Prata/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Técnicas de Química Sintética , Química Verde , Humanos , Masculino
16.
Biomed Pharmacother ; 118: 109187, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302425

RESUMO

Dan-hong injection (DHI) is extracted from Salvia miltiorrhiza (SM) and Carthamus tinctorius (CT) and is widely used for the treatment of cardiovascular diseases. Our previous results showed DHI could improve hemorheology in rats. Since complex cellular interactions such as inflammation and oxidative stress are believed to be implicated in the pathogenesis of cardiovascular events, investigation of such pathological factors will contribute substantially to the understanding of the features and mechanisms of DHI. Therefore, in this study we used a rat model of blood stasis to explore the overall effects of DHI by detecting twenty three indexes, which were related to inflammation, immune response, vascular endothelial function, myocardial energy metabolism, oxidative stress, platelet aggregation, liver and renal function. Meanwhile, the interaction between SM and CT was discussed by comparing the effects of each single herb. DHI could significantly decrease the serum contents of IL-1ß, TNF-α, IL-6, IL-8, IgM, IgG, IgA, MPO, hs-CRP, MDA, LDH, CK-MB, PAF, ALP and Cr, while elevate NO, SOD, TP and UA levels, indicating that DHI could inhibit inflammation and platelet aggregation, thereby relieving immune response and peroxidation, protecting vascular endothelial and organ function, and then prevent and treat cardiovascular diseases. In terms of compatibility, SM and CT showed complementary effects on markers of inflammatory and oxidative status, vascular endothelial damage and myocardial energy metabolism. On the other hand, they counteracted each other and SM reduced the side effects of creatinine caused by CT. This study contributes to comprehensively understand the pharmacodynamics effects and mechanism of DHI.


Assuntos
Carthamus tinctorius/química , Doença das Coronárias/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Salvia miltiorrhiza/química , Animais , Doença das Coronárias/sangue , Doença das Coronárias/imunologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Hemostasia/imunologia , Inflamação , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
17.
Am J Chin Med ; 47(5): 1113-1131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31352786

RESUMO

Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF. EASM positively alleviated oxidative stress by upregulating nuclear factor-erythroid 2-related factor 2 (Nrf2) and concomitantly downregulating NADPH oxidase 4 (Nox4) in the lungs of BLM-treated mice. This effect was also observed in an in vitro model of transforming growth factor beta 1 (TGF-ß1)-stimulated fibroblast activation. EASM reduced reactive oxygen species (ROS) generation in fibroblasts by stabilizing Nrf2 protein with promoting kelch-like ECH-associated protein 1 (Keap1) degradation. Nrf2 knockdown in the lungs of BLM-treated mice diminished the inhibitory effects of EASM on fibrosis, providing evidence in vivo to address the unique role of Nrf2. Additionally, EASM inhibited TGF-ß1/Smad3 signaling by downregulating protein kinase C delta (PKC-δ) and Smad3 phosphorylation (p-Smad3), which led to suppression of the TGF-ß1-induced fibrogenic response. These results indicate that EASM exhibits potent antifibrotic activity in vitro and in vivo, which might be associated with activation of Nrf2 pathway and inhibition of TGF-ß1/Smad3 pathway. Our findings support that EASM may act as an effective antifibrotic remedy for PF.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , NADPH Oxidase 4/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Salvia miltiorrhiza/química , Animais , Feminino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , NADPH Oxidase 4/genética , Fator 2 Relacionado a NF-E2/genética , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo
18.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2059-2064, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355561

RESUMO

To construct a quality management model for the whole industry chain of compound Danshen Tablets,and quality control system for all key links in the production of compound Danshen Tablets. In this paper,with salvianolic acid B as internal reference substance,three batches of mix standards were prepared,and three sets of relative correlation factors between salvianolic acid B and other phenolic acids were calculated in parallel. Finally,the correlation factors are obtained on average. The quality transfer process was studied by optimizing the concentration of Salvia miltiorrhiza extract. The results showed that RSD among three sets of relative correlation factors ranged between 1. 7%-4. 1%,with no significant difference between the quantitative result of two methods. In addition,the quality transfer study showed that with the rise of the concentration temperature,the content of phenolic acid components changed,which had a significant effect on the salvianolic acid B at more than 80 ℃. It was suggested to rationally control the concentration temperature during the industrial production. The results of this study provide a methodology for the establishment of the quality control system for the whole industry chain of compound Danshen Tablets,and quality control methods for the improvement of the quality of medicinal materials and finished medicine products.


Assuntos
Medicamentos de Ervas Chinesas/química , Hidroxibenzoatos/análise , Salvia miltiorrhiza/química , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Comprimidos
19.
Int J Mol Med ; 44(2): 457-468, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173197

RESUMO

Salvianolic acid B (Sal B) is a water­soluble active component of Danshen and has anti­atherosclerotic effects. The present study aimed to evaluate the cytoprotective effects of Sal B against hydrogen peroxide (H2O2)­induced oxidative stress damage in human umbilical vein endothelial cells (HUVECs) and investigate the underlying mechanisms. It was revealed that Sal B protected the cells from H2O2­induced damage, as indicated by MTT results showing enhanced cell viability and by flow cytometric analysis showing reduced apoptosis of cells challenged with H2O2. Furthermore, as an underlying mechanism, the enhancement of autophagy was indicated to be accountable for the decrease in apoptosis, as Sal B caused the upregulation of light chain 3­â…¡ and Beclin­1, and downregulation of p62 under H2O2­induced oxidative stress. Finally, Sal B increased the phosphorylation of AMP kinase (AMPK) and decreased the phosphorylation of mammalian target of rapamycin (mTOR), but had no effect on the phosphorylation of AKT. In conclusion, the present study revealed that Sal B protects HUVECs from oxidative stress, at least partially by promoting autophagy via activation of the AMPK pathway and downregulation of the mTOR pathway.


Assuntos
Antioxidantes/farmacologia , Benzofuranos/farmacologia , Células Endoteliais/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Antioxidantes/química , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Benzofuranos/química , Citoproteção/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Estresse Oxidativo/efeitos dos fármacos , Salvia miltiorrhiza/química
20.
Cancer Immunol Immunother ; 68(7): 1073-1085, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161238

RESUMO

Cryptotanshinone (CT), a purified compound initially isolated from the dried roots of Salvia militorrhiza. Bunge, exhibits cytotoxic antitumor effects on many tumors. We have shown that CT possesses the dual capacities to concomitantly inhibit the proliferation of lung cancer cells and promote the generation of antitumor immunity. In this study, we investigated whether CT could be used to treat hepatocellular carcinoma (HCC) using a mouse Hepa1-6 model. CT inhibited the proliferation of mouse hepatoma (Hepa1-6) cells in vitro by inducing Hepa1-6 cells apoptosis through the JAK2/STAT3 signaling pathway. In addition, CT activated macrophages and polarized mouse bone marrow-derived macrophages (BMM) toward an M1 phenotype in vitro, which depended on the TLR7/MyD88/NF-κB signaling pathway. Furthermore, CT significantly inhibited the growth of syngeneic Hepa1-6 hepatoma tumors, and, in combination with anti-PD-L1 cured Hepa1-6-bearing mice with the induction of long-term anti-Hepa1-6 specific immunity. Immunoprofiling of treated Hepa1-6-bearing mice revealed that CT-promoted activation of tumor-infiltrating macrophages and dendritic cells, induction of antitumor T cell response, and infiltration of effector/memory CD8 T cells in the tumor tissue. Importantly, the immunotherapeutic effects of CT and anti-PD-L1 depended on the presence of CD8 T cells. Thus, CT and anti-PD-L1 may provide an effective immunotherapeutic regimen for human HCC based on a combination of cytotoxic effects and induction of tumor-specific immunity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Fenantrenos/farmacologia , Receptor 7 Toll-Like/metabolismo , Imunidade Adaptativa/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Ativação Linfocitária , Macrófagos/imunologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fenantrenos/uso terapêutico , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Receptor 7 Toll-Like/imunologia , Resultado do Tratamento
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