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

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

doi:10.3390/ijms20205035

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.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by symmetric polyarthritis with swelling and pain at synovial joints [1]
We first investigated whether AD can ameliorate Freund’s complete adjuvant-induced arthritis (AA) (Figure 1A)
We found that AD treatment decreased the levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-17A), while it increased the level of anti-inflammatory cytokine IL-10 in the plasm of AA mice

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by symmetric polyarthritis with swelling and pain at synovial joints [1]. Emerging studies have demonstrated that neutrophils play critical roles in the initiation, progression, and perpetuation of RA [5]. Neutrophils granule proteins, such as myeloperoxidase (MPO) and neutrophil elastase (NE), are detected in high concentrations in RA synovial fluid, which are responsible for joint damage [6,7,8]. Numerous studies have illustrated that neutrophil extracellular traps (NETs) can promote auto-immunity and aggravate tissue damage [8,9]. Neutrophils depletion or functional inhibition significantly ameliorates joint damage and inflammation in an arthritis murine model [12]. Neutrophils serve as an important target of RA treatment

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Discussion

Conclusion