Ginsenoside F2 from the leaves of Panax ginseng alleviates DSS-induced ulcerative colitis: An in silico analysis and in vivo investigation

Panax ginseng, as one of the most important perennial industrial plant, has been widely cultivated in northern parts of China and Korea as a stimulant and dietary supplement. Recent research has suggested that ginsenoside F2 (GF2) possesses excellent anti-inflammatory effects. However, the impact of GF2 on colitis remains unclear. This study aimed to investigate the therapeutic effects of GF2 on acute colitis in mice and to further explore its inhibitory effects on the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomes in immortalized bone marrow-derived macrophages. GF2 alleviated clinical colitis symptoms, restored intestinal barrier function, and inhibited the NLRP3 signaling pathway in the colitis mouse model, thereby improving DSS-induced colitis. Further in vitro experiments confirmed that GF2 suppressed the activation of NLRP3 inflammasomes by reducing the expression of related proteins and inhibiting the assembly of NLRP3 inflammasomes. Notably, GF2 showed a more pronounced effect in blocking NLRP3 inflammasome assembly than in inhibiting protein expression. To further clarify the interactions between GF2 and NLRP3 inflammasomes, molecular modeling including density functional theory (DFT) calculations, molecular docking, and molecular dynamics simulations (MDs) was carried out. The docking and MDs results confirmed the stability of the complex at the active site. This study is the first to propose that GF2 may be useful as a potential functional food and natural medicine for the prevention and treatment of inflammatory bowel disease (IBD). • Ginsenoside F2 (GF2) was isolated from the leaves of Panax ginseng. • GF2 mitigates symptoms in mice with DSS-induced colitis. • GF2 suppresses the activation of NLRP3 inflammasomes in DSS mice. • GF2 inhibits inflammasome activation in iBMDMs.