A Novel Multiple-Network Analysis Integrating Metabolomics and Pharmacology for Mechanism Study of Medicine:A Case Study of CDD-2101 Against Constipation  

作　　者：Jingchun Shi Li Xiang Yan YLam Ziwan Ning Jie Liu Yaqi Li Yujuan Zhou Lixiang Zhai Chengyuan Lin Lin Zhu Zhaoxiang Bian 

机构地区：[1]Centre for Chinese Herbal Medicine Drug Development Limited,Hong Kong Baptist University,Hong Kong 999077,China [2]School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China [3]State Key Laboratory of Environmental and Biological Analysis,Department of Chemistry,Hong Kong Baptist University,Hong Kong 999077,China [4]Department of Medicine,School of Clinical Medicine,LKS Faculty of Medicine,The University of Hong Kong,Hong Kong 999077,China

出　　处：《Journal of Analysis and Testing》2024年第4期415-430,共16页分析检测(英文)

基　　金：Open access funding provided by Hong Kong Baptist University Library。

摘　　要：Constipation aff ects more than 14%of the global population with complex pathogenesis.Compound Traditional Chinese medicines(TCM),such as CDD-2101,a manufactured version of a time-tested TCM,hold great promise for constipation treatment due to the multiple-component-multiple-target strategy.Here,a novel multiple network analysis based on metabolomics and network pharmacology was developed to decipher the complex interplays between CDD-2101 and constipation.First,CDD-2101 alleviated constipation in a loperamide-induced acute constipation mice model and no adverse eff ect was observed.Then,fecal metabolomics and phytochemistry profi les were conducted by liquid chromatography-mass spectrometry analysis.The untargeted metabolomics built a metabolomic network related to signifi cantly modulated pathways during the constipation alleviation,including bile acid secretion,steroid hormone biosynthesis,glycerophospholipid metabolism,and linoleic acid metabolism.Based on the phytochemistry,network pharmacology predicted similar modulated pathways and built a hub-target network including retinoid X receptor alpha(RXRA),cytochrome P4501A1(CYP1A1),cytochrome P4501A2(CYP1A2),and phospholipase A2-IVA(PLA2G4).Third,integrated networks were built to select the key pathways and targets,as well as the key ingredients,including rhein,hesperetin,albifl orin,and magnolol from the TCM,which were corroborated by molecular docking,in vitro enzyme assays,and targeted metabolomics results.Finally,an integrated network was built to elucidate the multi-ingredient-multi-symptom linkage during the treatment.In conclusion,the novel multiple-network analysis revealed the complex“multi-component-multi-target-multi-pathway”mechanisms of CDD-2101 against constipation.Our work provides insight into the understanding of active compounds and pharmacological mechanisms,contributing to the development of natural medicines.

关 键 词：Metabolomics Network pharmacology Mass spectrometry CONSTIPATION MEDICINE 

分 类 号：TQ460.1[化学工程—制药化工]