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1.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
2.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1772-1778, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489060

RESUMO

Wogonin is a main effective component of Scutellaria baicalensis, with a significant anti-cancer activity. Recently, extensive studies focused on anti-cancer pharmacological effects of wogonin, but there were still a few studies on its molecular mechanism. Therefore, the molecular targets of its anti-cancer activity were still unclear. In this study, network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer. It indicated that Wnt/ß-catenin was a key pathway of wogonin on colorectal cancer. Then, pharmacology and molecular mechanism studies were performed according to network pharmacological results. Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480(P<0.001), with a concentration-dependent regularity in the range of 12.5-50 µmol·L~(-1). Additionally, wogonin could induce G_1 phase blocking of SW480 cells. Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/ß-catenin pathway. CTNNB1(ß-catenin), BIRC5(survivin) and GSK3 B were down-regulated significantly, while the expression level of BAX was up-regulated(P<0.05). In conclusion, wogonin could inhibit the proliferation of SW480 cells through Wnt/ß-catenin pathway. The feature protein CTNNB1(ß-catenin), BIRC5(survivin), GSK3 B and BAX were identified as the potential targets. This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin, which provided a theoretical basis for anti-colon cancer drug discovery and clinical application.


Assuntos
Neoplasias Colorretais , Quinase 3 da Glicogênio Sintase , Linhagem Celular Tumoral , Proliferação de Células , Flavanonas , Humanos , Via de Sinalização Wnt , beta Catenina
3.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3653-3661, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602937

RESUMO

For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).


Assuntos
Biofarmácia/classificação , Medicamentos de Ervas Chinesas/química , Flavanonas/química , Materia Medica/classificação , Humanos , Absorção Intestinal , Permeabilidade , Solubilidade
4.
Zhongguo Zhong Yao Za Zhi ; 44(24): 5513-5519, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-32237403

RESUMO

Gansu province,which spans the Yangtze river,is in the upper reaches of the Yellow river and located at the intersection of the Qinghai-Tibet plateau,the Inner Mongolia plateau and the Loess plateau. All of these areas are highly respected by doctors of all ages as they have enriched the resources of traditional Chinese medicines. In the interaction between the heavens and the earth,the interaction between the people and the future has been passed down to the present. As one of the abbreviations of Gansu province, " Long" is not only the symbol and representative of the Gansu region,but also the symbol of the authentic medicinal materials in Gansu. This paper sorts out the evolution of the name " Long" medicines,the development status and development limitations of " Long" medicines. It is believed that although the production areas of authentic medicinal materials in Gansu have changed in different historical periods,the core varieties have been used ever since. Today,with the great development of the Chinese medicine industry,Gansu province pays attention to the limitations of the current regional and technological competitiveness in the province,and gives full play to its own advantages,which can help the " Long" medicines stand out among the medicinal materials. Furthermore,it lays the foundation for the development of the industry and the application of high quality Chinese herbal medicines in clinical practice.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , China , Medicina Tradicional Chinesa , Tibet
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