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Preventive effect of dioscin against monosodium urate-mediated gouty arthritis through inhibiting inflammasome NLRP3 and TLR4/NF-κB signaling pathway activation: an in vivo and in vitro study.
Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2020-08-06 , DOI: 10.1007/s11418-020-01440-7
Jieru Han 1 , Guangyu Shi 2 , Wenhao Li 1 , Ying Xie 1 , Fuzhen Li 1 , Deyou Jiang 1
Affiliation  

Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1β, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1β. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKβ, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.



中文翻译:

薯蓣皂苷通过抑制炎症小体 NLRP3 和 TLR4/NF-κB 信号通路激活对单钠尿酸盐介导的痛风性关节炎的预防作用:体内和体外研究。

尿酸单钠 (MSU) 介导的炎症与痛风性关节炎 (GA) 密切相关。据报道,薯蓣皂苷是一种活性成分,具有抗炎特性。然而,薯蓣皂苷在 GA 中的作用及其潜在机制尚未完全了解。在本研究中,我们通过体内和体外实验研究了薯蓣皂苷对 MSU 诱导的 GA 的抗炎作用。组织病理学分析表明,薯蓣皂苷可减轻 GA 的严重程度,同时降低尿酸和肌酐水平。此外,MSU 诱导的 IL-1β、IL-6 和 TNF-α 水平升高通过给予小鼠和人类滑膜细胞中的薯蓣皂苷而降低。Western blotting结果提示薯蓣皂苷通过下调NLRP3蛋白表达抑制NLRP3的活化,含有半胱天冬酶募集结构域 (ASC)、cleaved-caspase-1 以及 IL-1β 的凋亡相关斑点样蛋白。此外,薯蓣皂苷显着降低细胞核中的 TLR4、骨髓分化初级反应基因 88 (MyD88)、p-IKKβ、p-p65 和 NF-κB p65 水平。重要的是,薯蓣皂苷通过电泳迁移率变动分析 (EMSA) 分析显着降低了 MSU 治疗小鼠的 NF-κB p65-DNA 活性。总之,薯蓣皂苷通过抑制炎症细胞因子的产生和炎症小体 NLRP3 和 TLR4/NF-κB 信号通路的激活,对 MSU 引发的炎症反应具有保护作用。上述研究结果表明薯蓣皂苷可能是治疗 GA 的潜在药物。此外,薯蓣皂苷显着降低细胞核中的 TLR4、骨髓分化初级反应基因 88 (MyD88)、p-IKKβ、p-p65 和 NF-κB p65 水平。重要的是,薯蓣皂苷通过电泳迁移率变动分析 (EMSA) 分析显着降低了 MSU 治疗小鼠的 NF-κB p65-DNA 活性。总之,薯蓣皂苷通过抑制炎症细胞因子的产生和炎症小体 NLRP3 和 TLR4/NF-κB 信号通路的激活,对 MSU 引发的炎症反应具有保护作用。上述研究结果表明薯蓣皂苷可能是治疗 GA 的潜在药物。此外,薯蓣皂苷显着降低细胞核中的 TLR4、骨髓分化初级反应基因 88 (MyD88)、p-IKKβ、p-p65 和 NF-κB p65 水平。重要的是,薯蓣皂苷通过电泳迁移率变动分析 (EMSA) 分析显着降低了 MSU 治疗小鼠的 NF-κB p65-DNA 活性。总之,薯蓣皂苷通过抑制炎症细胞因子的产生和炎症小体 NLRP3 和 TLR4/NF-κB 信号通路的激活,对 MSU 引发的炎症反应具有保护作用。上述研究结果表明薯蓣皂苷可能是治疗 GA 的潜在药物。利用电泳迁移率变动分析 (EMSA) 分析,薯蓣皂苷显着降低了 MSU 处理的小鼠的 NF-κB p65-DNA 活性。总之,薯蓣皂苷通过抑制炎症细胞因子的产生和炎症小体 NLRP3 和 TLR4/NF-κB 信号通路的激活,对 MSU 引发的炎症反应具有保护作用。上述研究结果表明薯蓣皂苷可能是治疗 GA 的潜在药物。利用电泳迁移率变动分析 (EMSA) 分析,薯蓣皂苷显着降低了 MSU 处理的小鼠的 NF-κB p65-DNA 活性。总之,薯蓣皂苷通过抑制炎症细胞因子的产生和炎症小体 NLRP3 和 TLR4/NF-κB 信号通路的激活,对 MSU 引发的炎症反应具有保护作用。上述研究结果表明薯蓣皂苷可能是治疗 GA 的潜在药物。

更新日期:2020-08-06
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