Anti-inflammatory and anti-arthritic properties of naringenin via attenuation of NF-κB and activation of the heme oxygenase ﴾HO﴿-1/related factor 2 pathway

Pharmacol Rep. 2017 Oct;69(5):1021-1029. doi: 10.1016/j.pharep.2017.03.020. Epub 2017 Apr 13.

Abstract

Background: Naringenin, a bioflavonoid present in various species of citrus fruit, tomatoes and grapes, has been shown to have various pharmacological effects. We evaluated the anti-arthritic potential of naringenin in formaldehyde-induced inflammation and complete Freund's adjuvant (CFA)-induced arthritis.

Methods: For both evaluations, rats were divided into groups of six. Different doses of naringenin (5, 10 and 20mg/kg) were used in the models. Body weight and the arthritic index were assessed. Biochemical and antioxidant parameters were determined. Naringenin dose-dependently reduced joint inflammation, decreasing the joint diameter and inflammatory cell infiltration.

Results: Naringenin-treated rats showed an improvement in the synovium redox status (down-regulation of malondialdehyde and glutathione and up-regulation of Catalase (CAT) and superoxide dismutase levels). Naringenin significantly reduced the level of the inflammatory marker TNF-α. Naringenin increased Nrf-2/HO-1 and reduced NF-κB mRNA levels in CFA-treated animal joints. Additionally, naringenin treatment decreased the expression of extracellular matrix degrading enzymes, such as matrix metalloproteinase (MMP-3 and MMP-9), in CFA-induced arthritic rats.

Conclusions: We conclude that naringenin exerts anti-arthritic effects by downregulating NF-κB and activating the Nrf-2/HO-1 pathway.

Keywords: Complete Freund’s adjuvant; NF-κB; Naringenin; Nrf-2/HO-1 pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis / chemically induced
  • Arthritis / drug therapy*
  • Dose-Response Relationship, Drug
  • Flavanones / administration & dosage
  • Flavanones / pharmacology*
  • Freund's Adjuvant / toxicity
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Indomethacin / administration & dosage
  • Indomethacin / pharmacology
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents
  • Flavanones
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Freund's Adjuvant
  • Heme Oxygenase-1
  • naringenin
  • Indomethacin