Ginsenoside Rb1 exerts therapeutic effects on ulcerative colitis through regulating the Nrf2/PIP2/NLRP3 inflammasome signaling pathway

Ginsenoside Rb1 (GRb1), a bioactive ingredient of Panax ginseng C. A. Meyer, has the effects of anti-tumor, anti-inflammation, and cardiovascular protection. The present study aims to explore the effects and potential mechanisms of GRb1 on UC. GRb1 suppressed the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL -6), and IL-1 beta in both cells and mice models. GRb1 showed antioxidant effects and inhibited NLR family pyrin domain 3 (NLRP3) inflammasome activation by decreasing ROS production and directly targeting Nrf2 to activate Nrf2/HO-1/Keap-1 signaling pathway. In addition, GRb1 suppressed pyroptosis by inhibiting inflam-masome activation and Ca2+ level through the calcium-related phosphatidylinositol 4,5-bisphosphate (PIP2) signaling pathway. For the DSS-induced UC mice model, GRb1 improved the length and pathological damage to the colon to repair intestinal barrier integrity via modulating the inflammatory response. Taken together, GRb1 has therapeutic effects on UC in vitro and in vivo through regulating the Nrf2/PIP2/NLRP3 pathway, suggesting that GRb1 targeting Nrf2 is a potential therapeutic target for the treatment of UC.