Amelioration of Acute Gastritis by Biling Weitong Granules: A Multi-Omics Analysis of Synergistic PI3K/AKT and NF-κB Pathway Regulation

Introduction Gastric diseases have become a global health challenge due to infectious agents and unhealthy lifestyles, with a notable trend of rising incidence among younger populations in recent years, including children and adolescents who increasingly suffer from gastric discomfort. Biling Weitong Granules, an improved formulation derived from the classical prescriptions "Jinlingzi Powder" and "Zuojin Pill", embodies the therapeutic principles of "unblocking and descending theory" and "qi-blood harmony theory" in spleen-stomach disease treatment. This compound demonstrates efficacy in regulating qi flow, activating blood circulation, harmonizing the stomach, and alleviating pain, making it clinically applicable for various acute and chronic gastric disorders. However, its precise pharmacological mechanisms remain incompletely elucidated. Methods The chemical components of Biling Weitong Granules were identified using UHPLC-Q-Orbitrap-MS technology. Subsequently, an acute gastritis mouse model was established by absolute ethanol induction, with histopathological damage to gastric tissues evaluated through H&E staining. An integrated analysis combining network pharmacology, metabolomics, and transcriptomics was then conducted to investigate the mechanism underlying the anti-acute gastritis effects of Biling Weitong Granules. The expression levels of PI3K, AKT, P50, P65, IKKα, IκBα and their phosphorylated forms were detected by Western blotting. Results This study identified a total of 125 compounds in Biling Weitong Granules through comprehensive analysis. Network pharmacology analysis revealed that the therapeutic effects against acute gastritis may be mediated through key pathways including "Apoptosis", "TNF signaling pathway", "JAK-STAT signaling pathway", and "PI3K-Akt signaling pathway". Furthermore, integrated metabolomics and transcriptomics analyses demonstrated that Biling Weitong Granules exert their therapeutic effects by regulating metabolic abnormalities of glutathione and other amino acids, consequently modulating critical cellular processes such as oxidative stress, inflammatory responses, and apoptosis. Western blot analysis revealed that the phosphorylation levels of p-PI3K, p-AKT, p-P65, p-P50, p-IKKα, and p-IκBα were reduced after treatment with Biling Weitong Granules. Conclusion Biling Weitong Granules (BLWTG) exert therapeutic effects against acute gastritis (AG) by modulating metabolic abnormalities of glutathione and other amino acids, thereby influencing multiple signaling pathways including "Apoptosis", "TNF signaling pathway", "JAK-STAT signaling pathway", and "PI3K-Akt signaling pathway". These findings reveal the complex mechanistic basis underlying the anti-AG effects of this traditional Chinese medicine.