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

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.

• Authors: Xiaohong Li, Kai Yuan, Qingqing Zhu, Qingyi Lu, Haixu Jiang, Mengmeng Zhu, Guangrui Huang, Anlong Xu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 20 (Oct 11 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31614480 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Diterpenes
• Lipopolysaccharides
• andrographolide

Topics

• Animals
• Ankle Joint (drug effects, immunology)
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology)
• Apoptosis
• Arthritis, Rheumatoid (drug therapy, immunology, pathology)
• Cells, Cultured
• Cytokines (drug effects, metabolism)
• Disease Models, Animal
• Diterpenes (administration & dosage, pharmacology)
• Extracellular Traps (drug effects, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Neutrophil Infiltration (drug effects)
• Neutrophils (cytology, drug effects, immunology)