Integrating Network Pharmacology and In Vivo Model to Investigate the Mechanism of Biheimaer in the Treatment of Functional Dyspepsia

Abstract

Objective. Biheimaer (BHM) is a hospital formulation for clinical treatment of dyspepsia and acid reflux, based on Compatibility Theory of Traditional Chinese Medicine. This study anticipated to elucidate the molecular mechanism of BHM against Functional dyspepsia via combined network pharmacology prediction with experimental verification. Methods. Based on network pharmacology, the potential active components and targets of BHM in the treatment of functional dyspepsia were explored by prediction and molecular docking technology. The results of protein–protein interaction analysis, functional annotation, and pathway enrichment analysis further refined the main targets and pathways. The molecular mechanism of BHM improving functional dyspepsia mice induced by L-arginine + atropine was verified on the basis of network pharmacology. Results. In this study, 183 effective compounds were screened from BHM; moreover, 1007 compound-related predicted targets and 156 functional dyspepsia-related targets were found. The results of enrichment analysis and in vivo experiments showed that BHM could regulate intestinal smooth muscle contraction to play a therapeutic role in functional dyspepsia by reducing the expression of NOS3, SERT, TRPV1, and inhibiting the inflammatory cytokine (IL-1β, TNF-α) to intervene the inflammatory response in mice. Conclusions. This study revealed the molecular biological mechanisms of the Traditional Chinese Medicine formulation of BHM in functional dyspepsia by network pharmacology and experimental verification, meanwhile provided scientific support for subsequent clinical medication.

Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice

“…L-Arg is the only natural substrate for NO synthesis in vivo . L-Arg and oxygen can synthesize NO under the action of specific NOS, which inhibits gastrointestinal motility and causes symptoms of dyspepsia ( 16 ). Intraperitoneal administration of L-Arg increases Ca 2+ in the cytoplasmic matrix, activates NOS, catalyzes L-Arg and oxygen to produce more NO, activates guanylate cyclase, catalyzes guanosine triphosphate to cyclic guanosine monophosphate, and causes gastrointestinal smooth muscle hyperpolarization and relaxation ( 2 , 17 ).…”