Effective materials and mechanisms study of Tibetan herbal medicine Lagotis integra W. W. Smith treating DSS-induced ulcerative colitis based on network pharmacology, molecular docking and experimental validation

• DOI: 10.1016/j.jep.2022.115800
• Publication Date: 2022-10-11T01:23:21Z
• Authors: Xinhong Wang; Chi Zhang; Lin Liu; Yuanhan Zhong; Yujie Wang; Fangyuan Liu; Jixiao Zhu; Zejing Mu; Shouwen Zhang; Xiaomin Wang; Guoyue Zhong; Jian Liang; Jinxiang Zeng
• Keywords: Docking (animal); Catalpol

Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat "Chi Ba" disease clinically, the symptoms of which are similar to ulcerative colitis (UC).To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC.The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking.The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II.For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.