Protective effects of Xiaoshi Lipi formula on gastric precancerous lesions via multi-target regulation of inflammation, oxidative stress, ferroptosis and apoptosis

Background: Xiaoshi Lipi formula, a traditional Chinese medicine, may alleviate Gastric precancerous lesion (GPL) progression through multi-target mechanisms. Objectives: To evaluate the protective effects of Xiaoshi Lipi formula on GPL and its underlying mechanisms. Methods: GPL was induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium deoxycholate. Animals were assigned to normal, model, positive control and low-, medium-, or high-dose Xiaoshi Lipi formula groups. Gastric pathology was assessed by HE and AB-PAS staining. Serum inflammatory cytokines (TNF-?, IL-6, IL-1?), gastric function markers (G-17, PG I, PG II, PGE2), oxidative stress indices (ROS, MDA, SOD, GSH), ferroptosis- and antioxidant-related proteins and apoptosis (TUNEL) were analyzed. Results: Xiaoshi Lipi formula markedly alleviated gastric mucosal atrophy and intestinal metaplasia and improved gastric function. In the medium-dose group, G-17, PG I and PGE2 increased by ~90%, 70% and 62%, respectively, while PG? decreased by ~40%. TNF-?, IL-6 and IL-1? were reduced by ~45%. ROS and MDA declined by ~48% and 50%, while SOD and GSH rose by ~38% and 83%. GPX4 and SLC7A11 were restored, Nrf2/HO-1 pathway activated and TUNEL-positive cells reduced by ~68%. Medium-dose effects were comparable to the positive control. Conclusion: Xiaoshi Lipi formula ameliorates GPL by targeting inflammation, oxidative stress and ferroptosis, supporting its potential in gastric cancer prevention.