Berberine attenuates arthritis in adjuvant-induced arthritic rats associated with regulating polarization of macrophages through AMPK/NF-κB pathway

Berberine (BBR) is a traditional folk medicine with excellent anti-inflammatory properties. This study aimed to investigate the anti-arthritic effects of BBR in adjuvant arthritis (AA) in rats and its regulatory role in the polarization of macrophages. Rats were immunized with Complete Freund's Adjuvant (CFA), and then BBR (40, 80, 160 mg/kg) was administered orally for 14 days. BBR significantly reduced paw swelling and arthritis global assessment as well as alleviated joint destruction and inflammatory cell infiltration. The index of the thymus and thymocyte proliferation were significantly reduced by BBR. Moreover, BBR treatment restrained the phagocytic function of macrophages and restored the balance of M1/M2 by reducing the levels of M1 cytokines (tumour necrosis factor-alpha, interleukin-1 beta, and interleukin-6), increasing the levels of M2 cytokines (interleukin-10 and transforming growth factor-beta 1), increasing the expression of arginase 1(Arg1) (M2 marker) and decreasing the expression of inducible nitric oxide synthase (iNOS) (Ml marker). BBR also downregulated the ratio of Th17/Treg cells. Further research on the adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK)/nuclear factor kappa B (NF-kappa B) pathway found that BBR upregulated the activity of AMPK, while it downregulated the expression of phospho-RelA (p-p65), phospho-NF-kappa-B inhibitor alpha (p-I kappa B alpha) and cyclooxygenase (COX)-2. Therefore, our findings suggest BBR has significantly therapeutic effects in AA rats by regulating the polarization of macrophages through the AMPK/NF-kappa B pathway.