Ginsenoside Rg1 alleviated experimental colitis in obesity mice by regulating memory follicular T cells via Bcl-6/Blimp-1 pathway

Abstract

The pathological mechanisms of ulcerative colitis (UC) are closely related with abnormal memory follicular helper T (mTfh) cell subsets and the Bcl-6/Blimp-1 signaling pathway. Ginsenoside Rg1 (G-Rg1) has been confirmed to exhibit therapeutic effects in obese mice with dextran sulfate sodium (DSS)-induced ulcerative colitis. The aim of this study was to investigate the mechanism of action of G-Rg1 in obese mice with UC by observing mTfh cell subsets and the Bcl-6/Blimp-1 signaling pathway. Obese mice with UC were treated with G-Rg1 at a dose of 200 mg/kg. Disease activity was assessed macroscopically and microscopically, and cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to analyze mTfh cell subsets, and Western blotting to assess protein expression related to the Bcl-6/Blimp-1 pathway. qPCR was used to detect the expression of Bcl-6/Blimp-1, and immunofluorescence was utilized to compare Bcl-6/Blimp-1 expression between different groups. G-Rg1 treatment ameliorated the symptoms of DSS-induced colitis, alleviated the pathological changes in the colonic tissue of obese mice with ulcerative colitis, and reduced the levels of inflammatory cytokines in these mice. Furthermore, flow cytometry analysis indicated that G-Rg1 modulated the balanceof mTfh cells subsets by increasing central memory Tfh (cmTfh) cells and decreasing effector memory Tfh (emTfh) cells, thereby mitigating ulcerative colitis in obese mice. qPCR results revealed the significant upregulation of Bcl-6 and the downregulation of Blimp-1 expression in the DSS group, which was effectively reversed by G-Rg1 treatment. These findings were further confirmed by Western blot and immunofluorescence assays. Collectively, the qPCR, Western blot, and immunofluorescence results demonstrated the pivotal role of the Bcl-6/Blimp-1 signaling pathway in the therapeutic process of G-Rg1 for ulcerative colitis in obese mice. Ginsenoside Rg1 alleviates experimental colitis in obese mice by modulating the proportion of mTfh cell subsets via the Bcl-6/Blimp-1 signaling pathway.