Verification of the mechanism of action of isoliquiritigenin derivatives on LPS-induced FLS cells in rheumatoid arthritis based on network pharmacology.

Isoliquiritigenin (ISL), which has a chalcone parent structure, has a variety of pharmacological effects. In this study, ISL was structurally modified to create 16 bromate derivatives of ISL. The structures of these derivatives were determined using 1H NMR and 13C NMR. An in vitro rheumatoid arthritis inflammation model was established using LPS-induced fibroblast-like synoviocytes (FLS). The survival, NO content and viability of derivatives bound to LPS were determined by Elisa assay of the expression of the relevant inflammatory factors TNF-α, IL-1 and IL-1β. Network pharmacology predicted the relevant targets and pathways of action of ISL in rheumatoid arthritis, which were experimentally validated by RT-PCR method and Western Blot method. The results showed that ISL-6 exerted anti-rheumatoid arthritis effects by reducing the expression of inflammatory factors TNF-α, IL-1 and IL-1β, activating the PI3K/AKT pathway, promoting AKT phosphorylation, and then affecting the expression of the downstream signaling molecule FOXO1, which is associated with inflammation.