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

Abstract

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

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia: Based on serum pharmacochemistry and network pharmacology

“…41 , 42 Studies have indicated that inflammatory marker levels are elevated in viral pneumonia, and YSDZ reduces the expression of TNF‐α, and IL‐1β inflammatory factors. 6 , 43 Thus, YSDZ could play a major role in the treatment of viral pneumonia by regulating the inflammatory response.…”

“…It has also demonstrated efficacy in preventing and treating respiratory diseases due to its heat-clearing, detoxifying, phlegm-dissolving, and cough-relieving properties. [6][7][8] The formulation utilizes specific herbs to replenish and promote the circulation of qi (vital energy) and blood, stabilize the spirit, expel wind, relieve external heat, dissolve phlegm, and tranquilize the spirit. YSDZ has demonstrated significant clinical efficacy in preventing and treating SARS-CoV-2 infection and was utilized in Tanzania's epidemic in 2020, marking a significant milestone in the international application of TCM against COVID-19.…”

“…The last two decades of clinical application and research have shown the potential efficacy of YSDZ in treating several mental health conditions, such as anxiety, fear, and insomnia. It has also demonstrated efficacy in preventing and treating respiratory diseases due to its heat‐clearing, detoxifying, phlegm‐dissolving, and cough‐relieving properties 6–8 . The formulation utilizes specific herbs to replenish and promote the circulation of qi (vital energy) and blood, stabilize the spirit, expel wind, relieve external heat, dissolve phlegm, and tranquilize the spirit.…”

“…In addition, it has been noted that the S protein of SARS-CoV-2 can attach to the C-type lectin receptor on the surface of DCs, facilitating viral invasion and exacerbating the body'sinflammatory response, this promotes the onset of an 'inflammatory factor storm' 41,42. Studies have indicated that inflammatory marker levels are elevated in viral pneumonia, and YSDZ reduces the expression of TNFα, and IL-1β inflammatory factors 6,43. Thus, YSDZ could play a major role in the treatment of viral pneumonia by regulating the inflammatory response.…”

Chuanxiong Renshen Decoction Inhibits Alzheimer’s Disease Neuroinflammation by Regulating PPARγ/NF-κB Pathway

“…Vanquish ultra-high performance liquid chromatograph (UHPLC) (Thermo Fisher Scientific, USA) was used in this study. 22 Using Waters ACQUITY UPLC BEH Amide liquid chromatography column (2.1 mm × 50 mm, 1.7 μm; Milford, MA, USA), the target compounds were divided. In liquid chromatography, the aqueous phase (Phase A) consists of 25 mmol/L ammonium acetate and 25 mmol/L ammonia water, while the organic phase (Phase B) is composed of acetonitrile.…”