Network-based pharmacological study of the mechanism of Baitouweng decoction in the treatment of ulcerative colitis through the NF-κB pathway.

BACKGROUND: Baitouweng decoction (BD) is a classic formula for the treatment of ulcerative colitis (UC) with remarkable efficacy and low recurrence rate, although the therapeutic mechanism is still unclear. To screen out the active components and study the mechanisms of BD treating UC. METHODS: A network pharmacology strategy was used to screen the active ingredients and pathways of action of BD for the treatment of UC, and the binding activity of the screened active ingredients to the core targets was examined by molecular docking with Autodock Vina software, a macrophage inflammation model was established, administration of BD and its screened active ingredients, determination of relevant inflammatory cytokine levels and expression of pathway-related proteins to verify the mechanism of action of BD in the treatment of UC. RESULTS: Forty-five active components of BD, 186 relevant targets of UC, and 67 core intersecting genes of BD and UC were screened. Enrichment analysis revealed that the molecular mechanisms of BD treatment of UC are associated with IL-17, TNF-α, and Toll-like receptor signaling pathways, and that these signaling pathways all point to NF-κB-based inflammatory signaling pathways. Molecular docking suggests that the active components of BD, epiberberine, β-sitosterol, and anemoside B4 have a strong affinity for targets such as MPO, NOS3, and PPARG. MPO, NOS3, and PPARG can affect cytokine secretion and protein expression directly or indirectly through the NF-κB signaling pathway. Cell Counting Kit-8 results showed that BD and the active ingredient, in a range of nontoxic concentrations, increased cell survival in a model of LPS-induced cellular inflammation. BD and active ingredients could decrease LPS-induced inflammation and the levels of TNF-α, PGE2, IL-17, iNOS, IL-1β, COX-2, and NO. On the other hand, BD and the active ingredient promoted the expression and inhibited the phosphorylation of p65 and IκBα in the NF-κB signaling pathway in LPS-induced inflammation. CONCLUSIONS: β-sitosterol, stigmasterol, quercetin, isorhamnetin, berberine, and anemoside B4 may be the material basis for BD treatment of UC, which exerts anti-inflammatory effects by regulating the expression of inflammatory factors and modulating the NF-κB signaling pathway.