Lariciresinol protects rats from complete Freund's adjuvant induced arthritis in rats via modulation of transforming growth factor‐β and nuclear factor kappa B pathway: An in vivo and in silico study

Rheumatoid arthritis (RA) is a severe inflammatory auto‐immune disorder affecting millions of people across the globe. The current therapeutic options are not adequate to address the complications of RA. Therefore, the present study was conducted to elucidate the protective effect of lariciresinol, a lignan, against Complete Freund's adjuvant (CFA)‐induced arthritis in rats. The results of the study showed that lariciresinol improves paw swelling and arthritic scores in rats as compared to CFA rats. Lariciresinol also showed a significant reduction in rheumatoid factor, C‐reactive protein, tumor necrosis factor‐α, interleukin (IL)‐17, and tissue inhibitor of metalloproteinases‐3 level with a simultaneous increase in IL‐4 level. The burden of oxidative stress was also reduced in CFA rats, as shown by reduced MDA levels and increased SOD and GPx after the administration of lariciresinol. In a Western blot analysis, lariciresinol showed a significant reduction of transforming growth factor‐β and nuclear factor‐κB (NF‐κB) protein levels in CFA rats. To understand the binding characteristic of lariciresinol with NF‐κB, molecular docking analysis was conducted, which showed Larciresinol interacted with the active site of NF‐κB. Our study demonstrated the significant protective effect of lariciresinol against RA via multi‐target action. Lericiresinol inhibited RA‐induced inflammation by maintaining the delicate balance of pro‐inflammatory and anti‐inflammatory cytokines. It exhibits a strong anti‐inflammatory effect against CFA rats via interfering with TGF‐α and NF‐κB.