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\begin{document}

\title{Paeoniflorin-6'-O-benzene sulfonate inhibits macrophage pyroptosis via
TLR4/ NLRP3/ GSDMD signaling pathway in adjuvant arthritis rats}



\author[1]{Li Xu}%
\author[1]{Han Wang}%
\author[1]{Qianqian Yu}%
\author[1]{Jinru Ge}%
\author[1]{Xianzheng Zhang}%
\author[1]{Dan Mei}%
\author[1]{Faqin Liang}%
\author[1]{Xiaoyu Cai}%
\author[1]{Yue Zhu}%
\author[1]{Jinling Shu}%
\author[1]{Ling-Ling Zhang}%
\author[1]{Wei Wei}%
\affil[1]{Anhui Medical University}%


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  \date{May 04, 2024}


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\begin{abstract}
Abstract Purpose. To investigate the mechanisms of macrophage pyroptosis
mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis
(AA) rats and the role of Paeoniflorin-6'-O-benzene sulfonate (CP-25).
Experimental Approach. AA model was induced in Wistar rats via complete
Freund's adjuvant. Normal group, AA model group, CP-25 (50 mg/kg) group
and MTX (0.5 mg/kg) group were included in this experiment. The
co-expression of TLR4 and NLRP3 and membrane expression of GSDMD and
NLRP3 in macrophages were detected by immunofluorescence assay. The
expression of TLR4, the ratio of macrophage pyroptosis and M1/2-type
macrophages were detected by Flow Cytomery. Cell morphology was observed
by scanning electron microscopy. The levels of IL-18 and IL-1\selectlanguage{greek}β \selectlanguage{english}cytokines
in plasma and supernatant of cultured macrophage were detected by ELISA.
The expression of TLR4, MyD88, NLRP3, Caspase-1, ASC and GSDMD in
macrophages was detected by Western Blot. Key Results. Macrophage
pyroptosis was found in AA rats; CP-25 has a therapeutical effect on AA
rats by improving the joint inflammation and reducing the pathological
process of the joints of AA rats; CP-25 can inhibit the pyroptosis of
macrophages by down-regulate the expression of TLR4, MyD88, NLRP3,
Caspase-1, ASC and GSDMD of macrophages in vivo; CP-25 inhibits LPS and
ATP-induced macrophages pyroptosis by inhibiting the activation of
TLR4/NLRP3/GSDMD signaling pathway in vitro. Conclusion and
Implications. Macrophage pyroptosis was mediated through
TLR4/NLRP3/GSDMD signaling pathway, and CP-25 can regulate macrophage
pyroptosis by inhibiting TLR4/NLRP3/GSDMD signaling pathway, thereby
improving synovitis in AA rats.%
\end{abstract}%



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