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Effects of evodiamine on ROS/TXNIP/NLRP3 pathway against gouty arthritis

Yuan Cheng1, XiaoPeng Huang2, Yi Tang3

  • 1TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China. chengyuan83@cdutcm.edu.cn.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|August 9, 2023
PubMed

Insights

Evodiamine (EVO) effectively reduced swelling and inflammation in gouty arthritis rats. It works by inhibiting the NLRP3 inflammasome pathway, offering a potential new treatment for gout.

Area of Science:

  • Pharmacology
  • Immunology
  • Biochemistry

Background:

  • Gouty arthritis is a painful inflammatory condition characterized by monosodium urate crystal deposition.
  • Current treatments for gout can have side effects, necessitating the search for novel therapeutic agents.

Purpose of the Study:

  • To investigate the anti-inflammatory effects of Evodiamine (EVO) in a rat model of acute gouty arthritis.
  • To elucidate the underlying molecular mechanisms of EVO's action, focusing on the NLRP3 inflammasome pathway.

Main Methods:

  • Acute gouty arthritis was induced in Sprague-Dawley rats using sodium urate injection.
  • Rats were treated with varying doses of EVO or colchicine (positive control).
  • Ankle swelling, histopathology, serum inflammatory markers (IL-1β, IL-18, TNF-α), oxidative stress markers (ROS, XOD, SOD, MDA), and NLRP3 inflammasome components (TXNIP, NLRP3, caspase-1, ASC) were assessed.

Main Results:

  • EVO significantly alleviated ankle swelling and reduced inflammatory cell infiltration in the synovial tissue.
  • EVO decreased serum levels of pro-inflammatory cytokines (IL-1β, IL-18, TNF-α) and oxidative stress markers (ROS, XOD, MDA), while increasing SOD activity.
  • EVO downregulated the protein expression of TXNIP, NLRP3, pro-caspase-1, cleaved caspase-1, and ASC, indicating NLRP3 inflammasome inhibition.

Conclusions:

  • Evodiamine demonstrates significant anti-inflammatory and anti-gout effects in an acute gouty arthritis rat model.
  • The therapeutic mechanism of EVO involves the inhibition of the NLRP3 inflammasome via regulation of the ROS/TXNIP/NLRP3 signaling pathway.
  • EVO represents a promising therapeutic candidate for managing gouty arthritis.
Keywords:
Anti-inflammatoryEvodiamine (EVO)NLRP3 inflammasomeOxidative stress

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