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

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 20 mg/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-alpha. Naringenin increased Nrf-2/HO-1 and reduced NF-kappa B 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-kappa B and activating the Nrf-2/HO-1 pathway. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.