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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

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Abstract

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.

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Acknowledgements

This study was supported by a grant from the National Natural Science Foundation of China (No. 81704055).

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Author notes

  1. Jieru Han and Guangyu Shi contributed equally to this study.

Authors and Affiliations

  1. Department of Synopsis of the Golden Chamber, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, 24 Heping Road, Harbin, 150040, Heilongjiang, People’s Republic of China

    Jieru Han, Wenhao Li, Ying Xie, Fuzhen Li & Deyou Jiang

  2. Department of Ultrasound Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, Heilongjiang, People’s Republic of China

    Guangyu Shi

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  1. Jieru Han
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  2. Guangyu Shi
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  3. Wenhao Li
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  6. Deyou Jiang
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Correspondence to Deyou Jiang.

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Han, J., Shi, G., Li, W. et al. 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. J Nat Med 75, 37–47 (2021). https://doi.org/10.1007/s11418-020-01440-7

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  • DOI: https://doi.org/10.1007/s11418-020-01440-7

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