Integrating metabolomics and network pharmacology to investigate Mu Jin Powder prevents ethanol-induced gastric ulcer in rats

Abstract

Ethnopharmacological relevance: Gastric ulcer (GU) is a common multifactorial gastrointestinal disorder, affecting millions of people worldwide. Mu Jin Powder (MJP), a renowned herbal pair, was recorded in Yizong Jinjian by Wu Qian during the Qing dynasty. This combination has been integrated into traditional Chinese medicine (TCM) prescriptions for gastrointestinal diseases, particularly GU, and has demonstrated significant results in modern medicine studies. However, the specific advantages of MJP for GU and its underlying mechanisms remain insufficiently understood, requiring further investigation.

Aim of the study: To assess the preventive effects of MJP on ethanol-induced gastric mucosal injury and elucidate its underlying mechanisms.

Materials and methods: This study was based on ethanol induced SD rat model to elucidate the pharmacological effects of MJP. The chemical components of MJP and the absorbed components in the serum of treated rats were identified by UPLC-Q-TOF-MS. Serum metabolomics and Network pharmacology were applied to investigate the potential mechanisms of MJP against GU, and the mechanistic pathways were verified through PCR and Western blot analyses.

Results: In vivo pharmacological experiments demonstrated that MJP significantly reduced ulcer area and improved the histopathological features of gastric tissues. Fifty-three chemical components were determined in MJP, and 18 absorbed components were detected in the serum of treated rats for the first time. Non-targeted serum metabolomics revealed 28 significantly altered differential metabolites, most of which were modulated and normalized by MJP. Comprehensive network pharmacology and metabolomics analyses indicated that MJP exerted anti-GU effects by intervening in 5 key target proteins (PTG2, CHRNA7, CA1, PTG1, CASP3, and AKT1) and regulating differential metabolites. PCR and Western blot analyses suggested that MJP may inhibit the PI3K/Akt/NF-κB pathway to prevent ethanol-induced gastric ulcers.

Conclusions: Mu Jin Powder effectively ameliorates ethanol-induced gastric ulcers in rats, potentially by inhibiting the PI3K/Akt/NF-κB pathway.

Keywords: Gastric ulcer (GU); Herb pair; Mu Jin Powder (MJP); PI3K/Akt/NF-κB; Serum metabolomics.