Shengjiang powder ameliorates gastric mucosal injury through activating SIRT1/FOXO1 anti-oxidative stress.

INTRODUCTION: This research sought to investigate the therapeutic efficacy and underlying mechanisms of Shengjiang Powder (SJP) in the context of chronic gastritis. METHODS: A rat model of gastric mucosal injury was induced by 1-methyl-3-nitroso-1-nitrosoguanidine (MNNG) and a 10% NaCl solution, followed by treatment with either Vitacoenzyme or SJP. Histopathological changes in gastric tissues were evaluated using hematoxylin-eosin staining. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay. Western blot (WB) analysis was performed to detect COX-2 expression. Immunohistochemistry was used to assess TFF1 and TFF2 expression. Serum metabolomics was conducted to identify differential metabolites and enriched pathways, while proteins related to the FOXO signaling pathway were further examined in vivo. WB analysis was used to detect SIRT1, FOXO1, and STAT3. CAT and SOD2 activities were measured using biochemical assays. Multiplex immunohistochemistry was used to examine SIRT1-FOXO1 co-localization and FOXO1 nuclear localization. For the in vitro experiments, normal human gastric epithelial cells were treated with MNNG to induce inflammatory injury, followed by SJP administration in the presence or absence of the SIRT1 inhibitor EX-527. RESULTS: SJP alleviated gastric mucosal injury, reduced serum IL-6 levels and COX-2 expression, and significantly increased TFF1 and TFF2 expression. Metabolomics analysis identified 13 differential metabolites. The targets of these metabolites were intersected with gastritis-related targets, yielding 522 overlapping targets that were significantly enriched in the FOXO signaling pathway. In vivo and in vitro experiments showed that SJP upregulated SIRT1 and FOXO1 expression, increased CAT and SOD2 activities, inhibited STAT3 expression, and promoted FOXO1 nuclear localization. EX-527 blocked the restorative effects of SJP on FOXO1 expression and antioxidant enzyme activities. CONCLUSION: SJP ameliorates gastric mucosal injury and inflammation, potentially through modulation of the SIRT1/FOXO1 axis.