Effect of Licorice Laxative Decoction on Th1/Th2 cell balance in ulcerative colitis based on the GPR41/43 signaling pathway

ZHANG Xueqin; GAO Shuang; ZHANG Zhiyun

doi:10.3969/j.issn.1002-7386.2025.05.004

Abstract：Objective To investigate the protective effect of Licorice Laxative Decoction(GCXX)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)in mice and to explore the possible underlying mechanisms in regulating the Th1/Th2 balance.Methods An in vivo acute UC model was induced in mice by libitum consumption of 7％DSS solution for 2 days.Mice were randomly divided into the 5-ASA group,GCXX group,DSS group,and control group.Except for the control group,all mice were induced with DSS.Those in the 5-ASA group,GCXX group,and DSS group were given to an oral gavage of 5-ASA,GCXX,and equal doses of distilled water,respectively.Disease activity index(DAI)and colonic mucosal damage index(CMDI)were assessed in mice.Hematoxylin and eosin(H&E)staining was used to assess colonic tissue damage.Serum inflammatory factor levels were detected by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was performed to detect the percentage of Th1 and Th2 cells in the colon tissue.Western blot was used to detect protein expressions of G protein-coupled receptor 41(GPR41)and G protein-coupled receptor 43(GPR43).Results Mice in the DSS group presented intestinal hemorrhage,ulceration,and intestinal adhesions.Pathological analysis also revealed the degeneration and necrosis of mucosal epithelial cells,and a large number of inflammatory cell infiltration in the submucosal layer.GCXX significantly alleviated DSS-induced morphology and histopathological damage of the colon in UC mice.Compared with those of the control group,mice in the DSS group presented significantly greater colon length,and higher DAI,and CMDI in the DSS group(P＜0.05).Compared with those of the DSS group,mice in the GCXX and 5-ASA groups presented significantly less colon length,and lower DAI and CMDI(P＜0.05).Compared with those of the control group,mice in the DSS group presented significantly higher serum IL-6,TNF-α and IL-4,but lower IFN-γ(P＜0.05).Compared with those of the DSS group,mice in the GCXX and 5-ASA groups presented significantly lower serum IL-6,TNF-α and IL-4,but higher IFN-γ(P＜0.05).Compared with those of the control group,mice in the DSS group presented significantly lower percentage of CD4+IFN-γ+Th1 cell subpopulation,but higher percentage of CD4+IL-4+Th2 cell subpopulation in the colon tissues(P＜O.05).Compared with the DSS group,mice in the GCXX and 5-ASA groups presented significantly higher percentage of Th1 cell subpopulation,but lower percentage of Th2 cell subpopulation in the colon tissues(P＜0.05).The protein expressions of GPR41 and GPR43 in the colon tissues was significantly lower in the DSS group than those of the control group(P＜0.05).The protein expressions of GPR41 and GPR43 in colon tissues of mice in the GCXX group was significantly higher than those of the DSS group(P＜0.05).Conclusion Licorice Laxative Decoction may regulate the Th1/Th2 imbalance by modulating the GPR41/43 signaling pathway,thus attenuating DSS-induced colonic mucosal injury,reducing epithelial cell degeneration/necrosis,and inhibiting the secretion of inflammatory factors.