Wu Qing-Hua, Li Bing-Tao, Zhu Shui-Lan, Xiao Xin, Zhang Xiao-Qing, Tu Jun
Jiangxi Province Key Laboratory of Tranditional Chinese Medicine Etiopathogenisis, Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory, Jiangxi University of Traditional Chinese Medicine Nanchang 330004, China Key Laboratory of Traditional Chinese Medicine Pharmacology of Jiangxi Province Nanchang 330004, China.
Jiangxi Province Key Laboratory of Tranditional Chinese Medicine Etiopathogenisis, Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory, Jiangxi University of Traditional Chinese Medicine Nanchang 330004, China.
Zhongguo Zhong Yao Za Zhi. 2020 Apr;45(8):1764-1771. doi: 10.19540/j.cnki.cjcmm.20191213.401.
The network pharmacology was used to explore the potential active ingredients and action mechanisms of Mongolian medicine Cymbaria in the treatment of type 2 diabetes. According to the literatures collected, Cymbaria component database was established to define important active ingredients and key targets for the anti-hyperglycemic effect to predict action mechanism by active ingredient screening and target prediction techniques. Molecular docking predicted binding activity of main active components with key targets in Cymbaria, then verified the action mechanism in vitro. The Cymbaria component database contained 177 chemical components, 90 chemical structures were confirmed, including 34 chemical components with effective targets. According to the prediction results from network pharmacology, 61 biological processes were significantly affected, such as fatty acid metabolism including PPARs signaling pathway, protein kinase activity and insulin signal pathway. Moreover, the key target proteins were Akt1 and TNFα and quercetin, luteolin and catalpol were the main active ingredients of Cymbaria. Molecular docking prediction showed that luteolin, quercetin and catalpol had a strong binding activity with Akt1; luteolin had strong binding activity but quercetin and catalpol had a certain binding activity with TNFα. Furthermore, catalpol showed hypoglycemic effects in vitro, which up-regulated p-Akt(Ser473)/Akt, PPARα and PPARδ levels and reduced FABP4 expression to regulate glycose and lipid metabolism for improving insulin sensitivity. The network pharmacology predicted that the hypoglycemic effect of Cymbaria was mainly related to anti-inflammatory and lipid regulation with a multi-component, multi-target manner. It provided a scientific view of hypoglycemic effect and action mechanism of Cymbaria for further study.
运用网络药理学探究蒙药肉苁蓉治疗2型糖尿病的潜在活性成分及作用机制。依据收集的文献,建立肉苁蓉成分数据库,以确定重要活性成分和降糖作用的关键靶点,通过活性成分筛选和靶点预测技术预测作用机制。分子对接预测肉苁蓉主要活性成分与关键靶点的结合活性,随后在体外验证作用机制。肉苁蓉成分数据库包含177种化学成分,其中90种化学结构得到确认,包括34种具有有效靶点的化学成分。根据网络药理学预测结果,61个生物学过程受到显著影响,如包括PPARs信号通路的脂肪酸代谢、蛋白激酶活性和胰岛素信号通路。此外,关键靶蛋白为Akt1和TNFα,槲皮素、木犀草素和梓醇是肉苁蓉的主要活性成分。分子对接预测表明,木犀草素、槲皮素和梓醇与Akt1具有较强的结合活性;木犀草素具有较强的结合活性,而槲皮素和梓醇与TNFα具有一定的结合活性。此外,梓醇在体外显示出降糖作用,其上调p-Akt(Ser473)/Akt、PPARα和PPARδ水平并降低FABP4表达,以调节糖脂代谢从而改善胰岛素敏感性。网络药理学预测肉苁蓉的降糖作用主要与抗炎和脂质调节有关,呈多成分、多靶点方式。它为进一步研究肉苁蓉的降糖作用及作用机制提供了科学依据。