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舞草中环烯醚萜苷对佐剂诱导关节炎大鼠 OPG/RANKL/NF-κB 信号通路的抗类风湿关节炎作用。

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.

机构信息

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, CAS, Qinghai, 810008, China.

Key Laboratory of Medicinal Animal and Plant Resources in Qinghai-Tibetan Plateau in Qinghai Province, Xining, 810008, China.

出版信息

J Ethnopharmacol. 2021 Feb 10;266:113402. doi: 10.1016/j.jep.2020.113402. Epub 2020 Sep 24.

Abstract

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 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.

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.

摘要

民族药理学相关性

糙苏(Benth.)Kudo. 已被用于治疗中医创伤出血、风湿、黄热病。

目的

本工作旨在评价糙苏总环烯醚萜苷(TIG)的抗类风湿关节炎(RA)活性及其作用机制。

方法

采用高效液相色谱法(HPLC)结合 7 种对照品(毛蕊花糖苷、氯管倍半萜苷、山栀苷甲酯、梓醇、7-epliamalbide、葛根素 C 和 lamalbide)分析 TIG 的化学成分。通过关节炎指数和足肿胀程度以及佐剂诱导关节炎(AIA)大鼠的组织病理学和 Micro-CT 分析研究 TIG 的抗类风湿关节炎作用。通过酶联免疫吸附试验(ELISA)和 Western blot 分别测定 TIG 对炎症细胞因子(IL-1β、TNF-α、IL-6、IFN-γ、IL-17 和 IL-10)水平的影响,以及 OPG/RANKL/NF-κB 通路的调节作用。

结果

TIG 可显著降低 AIA 大鼠的关节炎指数和足肿胀程度,减轻关节组织的炎症和骨破坏,减少血清中促炎细胞因子 IL-1β、TNF-α、IL-6、IFN-γ 和 IL-17 的产生,增加抗炎细胞因子 IL-10 的产生。此外,TIG 明显抑制了 IKK-α、IκB 和 p65 的磷酸化,降低了滑膜组织中 OPG/RANKL 的比值。

结论

TIG 对佐剂诱导的关节炎具有显著的抗 RA 活性,这可能归因于对炎症细胞因子 IL-1β、TNF-α、IL-6、IFN-γ IL-17 和 IL-10 的调节,以及对 OPG/RANKL/NF-κB 信号通路的抑制。

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