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

独一味环烯醚萜苷通过 OPG/RANKL/NF-κB 信号通路对大鼠佐剂性关节炎的抗类风湿关节炎作用

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作者:Xiaohui Zhao, Sirong Jiang, Qi Dong, Jun Dang, Zenggeng Liu, Hongping Han, Yanduo Tao, Huilan Yue

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.

Conclusion

TIG possessed significant anti-RA activities on adjuvant-induced arthritis, which might be ascribed to the regulation of inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ IL-17 and IL-10, as well as inhibition of OPG/RANKL/NF-κB signaling pathways.

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 adjuvant-induced arthritis (AIA) rats. The impacts of TIG on the level of inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ, IL-17 and IL-10), and the regulation of OPG/RANKL/NF-κB 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-1β, TNF-α, IL-6, IFN-γ 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-α, p-IκB and p-p65, and decreased the ratio of OPG/RANKL in the synovial tissues.

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