The Traditional Chinese Medicine Compound Hezi Qingyou Formula Controls the MAPK Signaling Pathway for Alleviating Gastric Ulcer Induced by Acetic Acid in Rats.

Abstract

In clinical practice, Hezi Qingyou Formula (HZQYF) has been observed to effectively alleviate clinical symptoms associated with gastri ulcers, though its precise mechanism of action remains unclear. To investigate the effects of HZQYF on gastric ulcers, we established a rat model of gastric ulcer and examined its impact on ulcer area, pathological changes, inflammatory cytokines, gastric repair factors, levels of T-superoxide dismutase (SOD), and malondialdehyde (MDA), as well as metabolites in gastric tissue and feces. The results demonstrated that HZQYF significantly reduced the gastric ulcer area and promoted gastric tissue repair in rats. It downregulated the phosphorylation of P-P38, P-JNK1/2, and ERK1/2 proteins in the mitogen-activated protein kinases (MAPKs) pathway, inhibited pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), enhanced the expression of gastric repair factors including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), trefoil factor family 2 (TFF2), and prostaglandin E2 (PGE2), reduced MDA content, and increased the activity of the antioxidant enzyme T-SOD, thereby suppressing inflammatory responses and ameliorating gastric mucosal damage. Metabolomic studies revealed that HZQYF effectively normalized 40 metabolites in gastric tissue through four key metabolic pathways and 39 metabolites in feces through five key metabolic pathways. Notably, it regulated taurine and hypotaurine metabolism, as well as phenylalanine metabolism, restoring metabolite levels to normal and ameliorating metabolic disorders in diseased rats. In conclusion, HZQYF promotes the healing of experimental gastric ulcers in rats through anti-inflammatory effects, activation of gastric repair factors, and normalization of gastric tissue metabolites, suggesting its potential therapeutic role in the treatment of gastric ulcers.