Identification of metabolites from the gut microbiota in hypertension via network pharmacology and molecular docking  

作　　者：Wenjie Zhang Yinming Zhang Jun Li Jiawei Tang Ji Wu Zicong Xie Xuanchun Huang Shiyi Tao Tiantian Xue 

机构地区：[1]Department of Cardiology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,No.5 Beixiange,Xicheng District,Beijing 100053,China [2]Graduate School,Beijing University of Chinese Medicine,Beijing,China [3]Department of Emergency,Yankuang New Journey General Hospital,Zoucheng,Shandong Province,China [4]School of Computer Science,Beijing University of Posts and Telecommunications,Beijing,China.

出　　处：《Bioresources and Bioprocessing》2024年第1期1324-1339,共16页生物资源与生物加工(英文)

基　　金：supported by the National Key Research and Development Program of China(No.2022YFC3500102).

摘　　要：Hypertension is the most prevalent cardiovascular disease,affecting one-third of adults.All antihypertensive drugs have potential side effects.Gut metabolites influence hypertension.The objective of this study was to identify antihypertensive gut metabolites through network pharmacology and molecular docking techniques and to validate their antihypertensive mechanisms via in vitro experiments.A total of 10 core antihypertensive targets and 18 gut metabolites that act on hypertension were identified.Four groups of protein metabolites,namely,CXCL8-baicalein,CXCL8-baicalin,CYP1A1-urolithin A,and PTGS2-equol,which have binding energies of−7.7,−8.5,−7.2,and−8.8 kcal-mol−1,respectively,were found to have relatively high affinities.Based on its drug-likeness properties in silico and toxicological properties,equol was identified as a potential antihypertensive metabolite.On the basis of the results of network pharmacology and molecular docking,equol may exert antihypertensive effects by regulating the IL-17 signaling pathway and PTGS2.A phenylephrine-induced H9c2 cell model was subsequently utilized to verify that equol inhibits cell hypertrophy(P<0.05)by inhibiting the IL-17 signaling pathway and PTGS2(P<0.05).This study demonstrated that equol has the potential to be developed as a novel therapeutic agent for the treatment of hypertension.

关 键 词：HYPERTENSION Gut microbiota METABOLITE Network pharmacology Molecular docking EQUOL 

分 类 号：R54[医药卫生—心血管疾病]