Ginkgetin Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Nuclear Factor Kappa B Pathway.

Ginkgetin is a biflavone isolated from Ginkgo biloba leaves. It has shown anti-inflammatory effects in colitis. However, its molecular mechanisms remain unclear. This study investigated the therapeutic effects of ginkgetin on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-treated Caco-2 cells. Inflammation, the integrity of the colonic epithelial barrier, and cellular damage were assessed via immunofluorescence, reverse transcription quantitative polymerase chain reaction, and Western blotting. Furthermore, p65 was overexpressed or knocked down to examine its involvement in the observed effects. Treatment with ginkgetin significantly attenuated weight loss, disease activity index, and histopathological damage in DSS-induced mice. It also downregulated pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), and upregulated tight junction proteins, such as zonula occludens-1 (ZO-1) and Occludin, in vivo and in vitro. Notably, ginkgetin inhibited p-p65 and C-X-C motif chemokine ligand 2 in colonic tissues and Caco-2 cells. Molecular docking, biotin pull-down, and cellular thermal shift assays suggested an interaction between ginkgetin and p65. p65 overexpression reversed the inhibitory effects of ginkgetin on LPS-induced inflammation and barrier disruption. p65 knockdown normalized LPS-induced alterations, downregulated pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β), and upregulated tight junction proteins (ZO-1 and Occludin). Notably, the addition of ginkgetin did not further improve the beneficial effects of p65 knockdown alone. These findings suggest that ginkgetin alleviated colitis by modulating inflammation and epithelial barrier dysfunction through the nuclear factor kappa B pathway. This study demonstrates the potential of ginkgetin as a therapeutic agent for colitis.