Amomum tsaoko extract from Nujiang alleviates DSS-induced colitis through inhibiting necroptosis

Necroptosis, a form of programmed cell death, plays a significant role in compromising the intestinal barrier and initiating intestinal inflammation. An analysis of data from the Gene Expression Omnibus (GEO) reveals a strong correlation between ulcerative colitis (UC) and the pathological mechanisms of necroptosis. Consequently, inhibiting necroptosis may offer a promising strategy for ameliorating UC. Cao Guo (CG), a traditional Chinese medicine extensively utilized in China for both dietary and medicinal purposes, is frequently included in classical prescriptions for UC treatment. However, the precise chemical constituents of CG and its potential therapeutic targets for UC remain inadequately characterized. In this study, we analyzed the chemical composition of CG, employed a classic necroptosis model to assess the anti-necroptosis activity of CG, and conducted validation using a mouse model of UC. Through bioinformatics analysis and other methodologies, we initially explored the potential targets of CG in UC treatment and conducted subsequent verification. The findings demonstrate that in an in vitro necroptosis model, CG significantly enhances cell morphology and survival rates, while concurrently inhibiting the phosphorylation of RIPK1, RIPK3, and MLKL. In a mouse model of UC, CG alleviates weight loss and the disease activity index (DAI), ameliorates intestinal histopathological conditions, and upregulates the expression of tight junction proteins, such as ZO-1 and Occludin. Concurrently, CG diminishes the distribution and expression of phosphorylated RIPK3 and MLKL. Bioinformatics analysis suggests that CG may inhibit necroptosis via the signal transducer and activator of transcription 3 (STAT3) pathway, a hypothesis preliminarily validated through experimental methods. These results indicate that CG may exert therapeutic effects on UC by inhibiting STAT3 phosphorylation and suppressing necroptosis.