Anxiolytic effect of YangshenDingzhi granules: Integrated network pharmacology and hippocampal metabolomics

• DOI: 10.3389/fphar.2022.966218
• Publication Date: 2022-10-31T06:33:05Z
• Authors: Shimeng Lv; Weibo Dai; Yan Zheng; Ping Dong; Yihong Yu; Yifan Zhao; Shiguang Sun; Dezhong Bi; Chuanguo Liu; Fabin Han; Jibiao Wu; Tingting Zhao; Yuexiang Ma; Feng Zheng; Peng Sun
• Keywords: anxiolytics; Pharmacology; 0301 basic medicine; 03 medical and health sciences; molecular dynamics simulation; YangshenDingzhi granules; network pharmacology; molecular docking; Therapeutics. Pharmacology; RM1-950; metabolomics; 3. Good health

Anxiety disorder is one of the most common mental diseases. It mainly characterized by a sudden, recurring but indescribable panic, fear, tension and/or anxiety. Yangshendingzhi granules (YSDZ) are widely used in treatment anxiety disorders, its active ingredients and underlying mechanisms not yet clear. This study integrates network pharmacology metabolomics to investigate potential mechanism action YSDZ rat model First, targets were screened pharmacology. Then, predictions verified molecular docking, dynamics western blotting. Metabolomics was identify differential metabolites metabolic pathways. All results integrated for comprehensive analysis. Network analysis found that Carotene, β-sitosterol, quercetin, Stigmasterol, kaempferol exert anxiolytic effects acting on IL1β, GABRA1, PTGS1, ESR1, TNF targets. Molecular docking showed all affinities lower than -5 kcal/mol, average -7.7764 kcal/mol. simulation RMSD 2.5 A, overall conformational changes proteins small, indicating small molecules formed stable complexes with proteins. The animal experiments exerts regulating GABRA1 TNF-α, ameliorating pathological damage hippocampal CA1, pathways such as thiamine, cysteine methionine metabolism, lysine biosynthesis degradation. Altogether, we reveal multiple through which anti-anxiety effects, may provide reference clinical application drug development.