Tangeretin Inhibits Oxidative Stress and Inflammation via Upregulating Nrf-2 Signaling Pathway in Collagen-Induced Arthritic Rats

Pharmacology. 2019;104(3-4):187-195. doi: 10.1159/000501163. Epub 2019 Jul 25.

Abstract

Background/aims: Tangeretin (TAN), a major phytochemical in tangerine peels and an important Chinese herb, has multiple biological properties, especially antioxidative and anti-inflammatory effects. However, the mechanisms remain unclear. Based on these findings, the aim of the present study was to assess the antioxidant and anti-inflammatory properties of TAN in bovine type II collagen-induced arthritis rats.

Methods: TAN (50 mg/kg) was given orally once daily for 14 days. The effects of treatment were evaluated by biochemical assay (articular elastase, myeloperoxidase, end products of lipid peroxidation [MDA], antioxidant enzyme, such as superoxide dismutase, catalase, glutathione), nitric oxide, and inflammatory cytokines (interleukin-1β [IL-1β], -IL-10, tumor necrosis factor-alpha [TNF-α], interferon-γ [IFN-γ], and prostaglandin E2 [PGE2]). The protective effects of TAN against rheumatoid arthritis (RA) were evident from the decrease in arthritis scoring. Furthermore, the Nrf-2 signaling pathway was assessed to illustrate the molecular mechanism.

Results: TAN had therapeutic effects on RA by decreasing the oxidative stress damage and regulating inflammatory cytokine expression, including suppression of the accumulation of MDA products, decreasing the IL-1β, TNF-α, IFN-γ, and PGE2 levels, enhancing the IL-10 and the activity of antioxidant enzymes, which was through upregulating Nrf-2 signaling pathway.

Conclusion: TAN might have potential as a therapeutic agent for the treatment of RA.

Keywords: Collagen-induced arthritis; Cytokines; Nrf-2; Oxidative stress; Tangeretin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / metabolism
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism
  • Catalase
  • Collagen / pharmacology*
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Flavones / pharmacology*
  • Glutathione / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Joints / drug effects
  • Joints / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Flavones
  • Interleukin-1beta
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Nitric Oxide
  • Collagen
  • Catalase
  • Superoxide Dismutase
  • Glutathione
  • tangeretin
  • Dinoprostone