Niga-ichigoside F1 alleviates DSS-induced ulcerative colitis by inhibiting the NF-κB pathway

Niga-ichigoside F1, an ursolic acid-type pentacyclic triterpenoid, possesses various pharmacological properties, including anti-tumor, anti-inflammatory, and antinociceptive potentials. However, its function and underlying mechanism in ulcerative colitis (UC) remain unknown. Hence, this study aimed to explore the effect of Nigaichigoside F1 on dextran sulfate sodium (DSS)-induced colitis. The predictive results of network pharmacology identified 311 common targets of Niga-ichigoside F1 and ulcerative colitis. The 4 highest-scoring genes were screened by the BottleNeck method and they were, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), protein kinase B gamma (AKT3), and phosphatidylinositol-4,5bisphosphate 3-kinase, catalytic subunit beta (PIK3CB). KEGG pathway analysis indicated that Niga-ichigoside F1 probably exerted a protective effect on UC through the nuclear factor-kappa B (NF-kappa B) pathways. Molecular docking results showed that Niga-ichigoside F1 had a high affinity for nuclear factor-kappa B-inhibitor of nuclear factor-kappa B (NF-kappa B-I kappa B) complex, with the lowest binding energy. Furthermore, our results in vivo showed that Niga-ichigoside F1 alleviated weight loss, colon shortening, disease activity index (DAI), and histological scoring in DSS-induced colitis mice. Moreover, Niga-ichigoside F1 decreased the levels of inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) and the expression of oxidative stress markers nitric oxide (NO), myeloperoxidase (MPO), and malonaldehyde (MDA) to mitigate inflammation and intestinal damage. Western blotting results evidenced that Nigaichigoside F1 intervention significantly regulated the NF-kappa B pathway. In conclusion, this study highlighted the potential of Niga-ichigoside F1 in ameliorating colitis, indicating its potential application as a functional food.