Anti-rheumatoid arthritis effects of iridoid glucosides from Lamiophlomis rotata (Benth.) kudo on adjuvant-induced arthritis in rats by OPG/RANKL/NF-κB signaling pathways

Ethnopharmacological relevance: Lamiophlomisrotata (Benth.) Kudo. has been used to treat trauma bleeding, rheumatism, yellow water disease in traditional Chinese medicine. Aim: The aim of this work was to evaluate the anti-rheumatoid arthritis (RA) activities and underlying mechanisms of the total iridoid glucosides (TIG) from Lamiophlomisrotata (Benth.) Kudo. methods: The chemical constituents of TIG was analyzed by high-performance liquid chromatography (HPLC) with seven reference compounds (penstemonoside, chlorotuberside, shanzhiside methyl ester, phloyoside, 7-epliamalbide, phlorigidoside C and lamalbide). The anti-rheumatoid arthritis effects of TIG were investigated by arthritis indexes and paw swelling degrees, as well as histopathological and Micro-CT analysis in adjuvantinduced arthritis (AIA) rats. The impacts of TIG on the level of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IFN-gamma, IL-17 and IL-10), and the regulation of OPG/RANKL/NF-kappa B pathways were determined by the ELISA and western blot, respectively. Results: TIG significantly reduced the arthritis indexes and paws swelling in AIA rats, attenuated the inflammation and bone destruction in joint tissues, reduced the generation of pro-inflammatory cytokines IL-1 beta, TNF-alpha, IL-6, IFN-gamma and IL-17, as well as increased the generation of anti-inflammatory cytokine IL-10 in serum. Moreover, TIG markedly inhibited the expression of p-IKK-alpha, p-I kappa B and p-p65, and decreased the ratio of OPG/RANKL in the synovial tissues. Conclusion: TIG possessed significant anti-RA activities on adjuvant-induced arthritis, which might be ascribed to the regulation of inflammatory cytokines IL-1 beta, TNF-alpha, IL-6, IFN-gamma IL-17 and IL-10, as well as inhibition of OPG/ RANKL/NF-kappa B signaling pathways.