Palmatine ameliorates N‐methyl‐N'‐nitrosoguanidine‐induced chronic atrophic gastritis through the STAT1/CXCL10 axis

Abstract Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti‐inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N‐methyl‐N'‐nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose‐dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA‐seq and western blot revealed that PAL significantly improved IL‐17, TNF, and NF‐kappa B inflammation‐related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL‐17, TNF‐α, and p‐p65 expression. In conclusion, PAL was proposed to mitigate MNNG‐induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG.