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. 2024 Feb;30(2-4):66-78.
doi: 10.1177/17534259241255439. Epub 2024 May 23.

Myricetin reduces neutrophil extracellular trap release in a rat model of rheumatoid arthritis, which is associated with a decrease in disease severity

Yiqin Shu  1 , Rui Yang  1   2 , Huijie Wen  1 , Qiannan Dong  1   2 , Zhiqi Chen  1 , Yang Xiang  1   2   3 , Hao Wu  1   2   3
Affiliations

Myricetin reduces neutrophil extracellular trap release in a rat model of rheumatoid arthritis, which is associated with a decrease in disease severity

Yiqin Shu et al. Innate Immun. 2024 Feb.

Abstract

Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation and severe disability. However, there is a lack of safe and effective drugs for treating RA. In our previous study, we discovered that myricetin (MC) and celecoxib have a synergistic effect in the treatment of RA. We conducted in vitro and in vivo experiments to further investigate the effects and mechanisms of action of MC. Our findings demonstrated that MC treatment effectively reduced the release of neutrophil extracellular traps (NETs) and alleviated the inflammatory response in RA. Mechanistic studies showed that MC prevents the entry of PADI4 and MPO into the cell nucleus, thereby protecting DNA from decondensation. In a rat arthritis model, MC improved histological changes in ankle joints and suppressed NET-related signaling factors. In conclusion, MC protects the ankle joints against arthritis by inhibiting MPO and PADI4, thereby reducing NET release. The pharmacological mechanism of MC in RA involves the inhibition of NET release.

Keywords: Neutrophil extracellular traps; myeloperoxidase; myricetin; peptidylarginine deiminase 4; rheumatoid arthritis.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Network pharmacological study of MC for rheumatoid arthritis (RA).
Figure 2.
Figure 2.
MC can directly interact with both MPO and PADI4 proteins.
Figure 3.
Figure 3.
In neutrophils, MC inhibits NETosis by inhibiting the entry of PADI4 and MPO into the nucleus.
Figure 4.
Figure 4.
MC treatment ameliorates arthritis in rats with collagen-induced arthritis (CIA).
Figure 5.
Figure 5.
MC inhibits NE expression and histone 3 citrullination in CIA rats.
Figure 6.
Figure 6.
Mechanisms associated with the inhibition of NET release in rheumatoid arthritis by myricetin.
See this image and copyright information in PMC

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