Ginsenoside Rg3 Alleviates Complete Freund's Adjuvant-Induced Rheumatoid Arthritis in Mice by Regulating CD4+CD25+Foxp3+Treg Cells

Ginsenoside Rg3 (GRg3) is one of the major bioactive ingredients of ginseng, which is not only used as a herbal medicine but also used as a functional food to support body functions. In this study, the beneficial effects of GRg3 on rheumatoid arthritis (RA) mice was evaluated from anti-inflammatory and immunosuppressive aspects. The footpad swelling rate, pathological changes of the ankle joint, and levels of tumor necrosis factor alpha, interleukin 6, interleukin 10, and tumor necrosis factor beta were used to assess the anti-inflammatory effect of GRg3 on RA mice. Flow cytometric analysis of CD4(+)CD25(+)Foxp3(+) Treg cell percentage and metabolomic analysis based on gas chromatography-tandem mass spectrometry were used to assess the immunosuppressive effect and underlying mechanisms. GRg3 exhibited anti-inflammatory and immunosuppressive effects on RA mice. The potential mechanisms were related to regulate the pathways of oxidative phosphorylation and enhance the function of CD4(+)CD25(+)Foxp3(+) Treg cells to maintain peripheral immune tolerance of RA mice. These findings can provide a preliminary experimental basis to exploit GRg3 as a functional food or an effective complementary for the adjuvant therapy of RA.