Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis-NETosis Balance of Neutrophils

穿心莲内酯通过调节中性粒细胞凋亡-NETosis 平衡改善类风湿关节炎

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作者:Xiaohong Li, Kai Yuan, Qingqing Zhu, Qingyi Lu, Haixu Jiang, Mengmeng Zhu, Guangrui Huang, Anlong Xu

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.

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