Integrating network analysis and experimental validation to reveal the ferroptosis-associated mechanism of velvet antler in the treatment of chronic atrophic gastritis

Quan Liao^a, Zhenzhen Guo^b, Chenchun Ding^a, Renjie Zuo^a, Guoyan Liu ^a,b*

^a Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China

^b School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China

Chronic atrophic gastritis (CAG) is precancerosis with limited treatment options. This study investigated the therapeutic effects of velvet antler (VA), a traditional natural medicine, on CAG, with a focus on ferroptosis. In vivo experiments demonstrated the efficacy of VA in alleviating CAG, and network pharmacology analysis revealed its involvement in related terms, including inflammation, oxidative stress, and cell proliferation. Analyses further confirmed the modulation of ferroptosis by VA, particularly via the Keap1-Nrf2/HO-1/GPX4 pathway. In vitro assays supported these findings, demonstrating the ability of VA to reduce methylnitronitrosoguanidine-induced inflammation, oxidative stress, and ferroptosis in GES-1. This study provides a basis for exploring VA as a potential treatment for CAG, and offers new therapeutic strategies targeting ferroptosis.