Revealing the Mechanism of Chang-Shuang-Li-Zhong Powder in theTreatment of Ulcerative Colitis based on Network PharmacologyApproach

INTRODUCTION: Chang-shuang-li-zhong (CSLZ) powder is a traditional Chinese medicine (TCM) compound used for the management of inflammatory bowel disease (IBD) in China, yet its molecular mechanisms remain unclear. This study aimed to elucidate the pharmacological mechanisms of CSLZ in ulcerative colitis using an integrated network pharmacology approach. METHODS: The anti-inflammatory effects of CSLZ were assessed in vitro using LPS-activated RAW264.7 macrophages and in vivo using a dextran sulfate sodium (DSS)-induced chronic colitis mouse model. RESULTS: CSLZ treatment significantly alleviated colitis severity, evidenced by improved colon length, reduced disease activity scores, attenuated spleen enlargement, and decreased histological damage. It downregulated pro-inflammatory cytokines (IL-1β, IL-6) at both mRNA and protein levels in the mouse colon. In LPS-activated macrophages, CSLZ reduced mRNA expression of iNOS, TNF-α, IL-1β, and IL-6, and suppressed secretion of NO, IL-1β, and IL-6. Network pharmacology combined with experimental validation showed that CSLZ inhibited the phosphorylation of Akt, p38, ERK, and JNK in both cellular and animal models. DISCUSSION: These findings demonstrate that CSLZ exerts its anti-inflammatory effects primarily by suppressing the PI3K/Akt and MAPK signaling pathways. This aligns with and mechanistically explains its established clinical utility, positioning CSLZ as a promising multi-target therapeutic strategy for colitis. A limitation of the study is the correlative nature of the mechanistic evidence, warranting further direct genetic validation. CONCLUSION: CSLZ alleviates colitis-associated inflammation by inhibiting the PI3K/Akt and MAPK pathways, underscoring its potential as a novel therapeutic agent for ulcerative colitis.