Zhang, Ji (J);Xie, Jing (J);Niu, Zhiqiang (Z);You, Long (L);Liu, Yanan (Y);Guo, Rui (R);Yang, Guigui (G);He, Ziliang (Z);Shen, Ting (T);Wang, Honggang (H);Yan, Qi (Q);Hu, Weicheng (W);

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J Ginseng Res.2025 Feb 10;49(3):282-293.doi:10.1016/j.jgr.2025.02.001

Abstract

BACKGROUND: Ginsenoside Rg2 (G-Rg2), a major active compound of , 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.