Ginsenoside Rg2, a principal effective ingredient of Panax ginseng, attenuates DSS-induced ulcerative colitis through NF-κB/NLRP3 pathway
Ji Zhang, Jing Xie, Zhiqiang Niu, Long You, Yanan Liu, Rui Guo, Guigui Yang, Ziliang He, Ting Shen, Honggang Wang, Yan Qi, Weicheng Hu
Abstract
Background: , exhibits a wide range of pharmacological properties, including anticancer, antioxidant and neuroprotective effects. However, the mechanisms by which G-Rg2 mitigates ulcerative colitis (UC) have not been clearly elucidated. Aims: In the present study, we aimed to elucidate the underlying mechanisms by which G-Rg2 mitigated UC. Methods: In this study, we investigated the efficacy of G-Rg2 in ameliorating dextran sulfate sodium (DSS)-induced UC and its potential mechanisms using a DSS-induced UC mouse model and Lipopolysaccharides (LPS)/nigericin (Nig)-induced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation on immortalized bone marrow-derived macrophages (iBMDMs). Results: Oral administration of G-Rg2 at doses of 10 and 20 mg/kg significantly mitigated weight loss, normalized food and water intake, and improved colon histopathology in DSS-induced UC mice. G-Rg2 also restored mRNA expression levels of occludin, claudin-3, zona occluden (ZO)-1 and mucin 2, thereby enhancing intestinal barrier integrity. G-Rg2 significantly suppressed the nuclear translocation of p65, the subunit of nuclear factor kappa-B (NF-κB), as well as downregulated NLRP3, cleaved IL-1β and caspase1 p20 expression induced by LPS/Nig in iBMDMs. Conclusion: G-Rg2 effectively reduced colon inflammation in DSS-induced UC mice and diminishes inflammatory responses under LPS/Nig conditions by regulating NF-κB/NLRP3 pathway, thereby inhibiting NLRP3 inflammasome activation, which may serve as a potent therapeutic agent for UC.