Polysaccharide extract from Isatidis Radix inhibits multiple inflammasomes activation and alleviate gouty arthritis

被引:34
作者
Ren, Lutong [1 ,2 ,3 ,4 ]
Li, Qiang [2 ,3 ]
Li, Hui [1 ,2 ,3 ]
Zhan, Xiaoyan [2 ,3 ]
Yang, Ruichuang [5 ]
Li, Zhiyong [2 ,3 ]
Fang, Zhie [2 ,3 ]
Liu, Tingting [2 ,3 ]
Wei, Ziying [1 ,2 ,3 ]
Zhao, Jia [2 ,3 ]
Lin, Li [2 ,3 ]
Mou, Wenqing [2 ,3 ]
Dai, Wenzhang [2 ,3 ]
Bai, Zhaofang [2 ,3 ]
Xu, Guang [2 ,3 ,6 ]
Cao, Junling [1 ,7 ]
机构
[1] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Hepatol, Med Ctr 5, Beijing, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, China Mil Inst Chinese Mat, Med Ctr 5, Beijing, Peoples R China
[4] Chinese Peoples Liberat Army Gen Hosp, Natl Clin Res Ctr Infect Dis, Med Ctr 5, Beijing, Peoples R China
[5] Inner Mongolia Peoples Hosp, Dept Pharm, Hohhot, Peoples R China
[6] Beijing Univ Chinese Med, Dongfang Hosp, Dept Pharm, Beijing, Peoples R China
[7] Capital Med Univ, Sch Chinese Med, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
Isatidis Radix polysaccharide; MSU-induced gout; NLRP3; inflammasome; NLRP3; INFLAMMASOME; SUPPRESSOR;
D O I
10.1002/ptr.7514
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
摘要
The polysaccharide extract from Isatidis Radix exhibits potent antiinflammatory and antiviral activities, but the mechanism of Isatidis Radix polysaccharide (IRP) remains obscure. Herein, we reported that IRP blocked the activation of nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, leading to the inhibiting of caspase-1 cleavage and IL-1 beta secretion. Mechanistically, IRP did not inhibit NLRP3 inflammasome through suppressing mitochondrial reactive oxygen species (mtROS) production. However, IRP can significantly suppress the oligomerization of apoptosis-associated speck-like protein (ASC) and subsequently block the formation of inflammasome. Next, we evaluate the role of IRP in monosodium urate (MSU)-induced gout in vivo which is a NLRP3-associated disease. We also observed that oral administration of IRP can reduce the increased ankle thickness and the secretion of IL-1 beta, IL-18, IL-6, TNF-alpha and MPO of the mouse ankle joints caused by MSU crystals. Furthermore, flow cytometry analysis highlighted a significant modulation of T helper 17 cells (Th17)/regulatory T cells (Treg) following IRP treatment in MSU induced gout. Overall, our findings suggest that IRP has comprehensive and potent antiinflammatory effects and provide a reasonable therapeutic strategy in preventing inflammasome-associated diseases, such as inflammatory gouty arthritis.
引用
收藏
页码:3295 / 3312
页数:18
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