Macrophage Polarization Towards M2 Phenotype by Curcuminoids Through NF-κB Pathway Inhibition in Adjuvant-Induced Arthritis

Macrophage polarization is decisive for homeostasis maintenance and tissue repair. Anti-inflammatory properties of curcumin (CUR) have been demonstrated in several studies. It used in the treatment of bone disorders including rheumatoid arthritis. The present study aims to explore the potential mechanisms of curcumin on macrophage polarization, expression, activation, and cytokine secretion in adjuvant-induced arthritis as well as its possible role in enhancing the therapeutic action of methotrexate (MTX) together with minimizing MTX initiated side-effects. Rats were divided into eight groups as follows; Control group, MTX group: was weekly injected with MTX, CUR group: was treated with a daily oral dose of curcumin, MTX + CUR group: was treated with both methotrexate and curcumin, Adjuvant arthritis group (AIA): was injected with complete Freund's adjuvant for arthritis induction, AIA/MTX group: arthritic rats treated with methotrexate, AIA/CUR group: arthritic rats treated with curcumin and AIA/MTX + CUR: arthritic rats treated with both methotrexate and curcumin. Paw swelling, haematological analysis, immunological studies, histological observations and quantitative immunohistochemical investigations were performed. The present results showed that treating arthritic rats with curcumin either alone or in combination with methotrexate resulted in amelioration in paws inflammation, growth rate, absolute and relative spleen weights, and haematological analyses. Antinuclear antibodies, IL-1 beta, IL-8, IL-10, NF-kappa B levels, and CD68 + joint expression were also ameliorated. The microscopic examination of joint and spleen showed more improvement as apparently normal tissues in treated groups. It can be concluded that curcumin seems to be most promising in regulating macrophage expression, activation, cytokine secretion, and polarization, thus providing a novel insight in the application of curcumin-based treatments.

Automated summary

This study aimed to explore the potential mechanisms of curcumin on macrophage polarization, expression, activation, and cytokine secretion in adjuvant-induced arthritis and its role in enhancing the therapeutic action of methotrexate while minimizing side effects. The results showed that treating arthritic rats with curcumin, either alone or in combination with methotrexate, resulted in improvement in paw inflammation, growth rate, spleen weights, and hematological analyses. Curcumin may have a promising role in regulating macrophage expression, activation, cytokine secretion, and polarization.