Evodiamine attenuates adjuvant-induced arthritis in rats by inhibiting synovial inflammation and restoring the Th17/Treg balance.

Abstract

OBJECTIVES:

Evodiamine (Evo) possesses strong anti-inflammatory activity. In this study, we determine the antiarthritic effect of Evo.

METHODS:

Evo was administered to rats with adjuvant-induced arthritis (AA). We evaluated arthritis symptoms & histopathological changes and measured inflammatory cell infiltration, pro-inflammatory cytokine production and Th17 & Treg percentages in arthritic rats.

KEY FINDINGS:

Evo significantly improved the clinical signs of AA in rats, including decreases in paw swelling, the polyarthritis index and the number of swollen paw joints. Based on the histopathological analysis, Evo improved synovial inflammation and bone injury by inhibiting inflammatory cell infiltration, synoviocyte proliferation, pannus formation and cartilage erosion. Furthermore, the numbers of synovial CD3+ or CD68+ inflammatory cells were reduced, and the elevated levels of tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6 were restored to control levels by the Evo treatment. In addition, Evo therapy regulated the abnormal differentiation of Treg and Th17 cells, decreasing IL-17 production and increasing IL-10 levels. Finally, Evo inhibited Stat3 phosphorylation and induced Stat5 phosphorylation in rats with AA.

CONCLUSIONS:

Based on our results, Evo is a promising antiarthritic agent, potentially due to its inhibitory effect on synovial inflammation and regulatory effects on Treg and Th17 differentiation.

• Authors: Hui Zhang, Li Yin, Ming Lu, Jun Wang, Ye-Tian Li, Wei Lu Gao, Zong-Sheng Yin
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 72 Issue 6 Pg. 798-806 (Jun 2020) ISSN: 2042-7158 [Electronic] England
• PMID: 32056223 (Publication Type: Journal Article)
• Copyright: © 2020 Royal Pharmaceutical Society.

Chemical References

• Il6 protein, rat
• Interleukin-6
• Quinazolines
• STAT3 Transcription Factor
• STAT5 Transcription Factor
• Stat3 protein, rat
• Stat5a protein, rat
• Tumor Necrosis Factor-alpha
• Interleukin-10
• evodiamine

Topics

• Animals
• Arthritis, Experimental (drug therapy)
• Interleukin-10 (metabolism)
• Interleukin-6
• Joints (pathology)
• Male
• Quinazolines (pharmacology)
• Rats
• Rats, Inbred Lew
• STAT3 Transcription Factor
• STAT5 Transcription Factor
• Synovial Membrane
• Synovitis (drug therapy)
• T-Lymphocytes, Regulatory (drug effects)
• Th17 Cells (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)