RESUMO
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.
RESUMO
Objective: To analyze and test the effect of Rhizoma phragmitis and Rhizoma curcumae on the network pharmacology of MAPK (mitogen-activated protein kinase) and TNF (tumor necrosis factor) signaling channels and inflammatory factor target gene regulation in successful modeling of chronic atrophic gastritis rats. Methods: Rats with chronic atrophic gastritis that were modeled successfully were randomly divided into control and study groups and were treated with conventional western medicine or Rhizoma phragmitis and Rhizoma curcumae, respectively. The pharmacological mechanism of action and efficacy were evaluated. Results: The treatment efficiency was 76.32% and 97.37% in the control and study group, respectively. After treatment, the serum tumor necrosis factor-α (TNF-α) and serum malondialdehyde (MDA) levels in the study group were lower than those in the control group and the serum epidermal growth factor (EGF) and superoxide dismutase (SOD) levels in the study group were higher than those in the control group (P < 0.05); the pain behavioral scores in the study group were lower than those in the control group, and the free acid quantity and total acid quantity in the study group were higher than those in the control group (P < 0.05); the serum MTL index in the study group was higher than that in the control group, and the serum gastrin (GAS) and pepsinogen I (PG I) indices in the study group were lower than those in the control group (P < 0.05); the number of 24-hour reflux in the study group was less than that in the control group (P < 0.05), and the longest reflux time in the study group was lower than that in the control group (P < 0.05). Conclusion: Based on the network pharmacological results, Rhizoma phragmitis and Rhizoma curcumae will modulate MAPK, TNF signaling circuits, and inflammatory factor target genes in the chronic atrophic gastritis rat model. This treatment protocol is efficient and beneficial to enhance the gastric function of the chronic atrophic gastritis rat model, while it can alleviate the inflammatory response and significantly reduce the number and duration of reflux, which is a safe and reliable treatment modality.