Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway.

ABSTRACT

BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear. AIM: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model. METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1ß, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3. RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1ß, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1ß, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both). CONCLUSION: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.