School of Pharmacy, Bengbu Medical College, No.2600, Donghai Avenue, Bengbu 233000, Anhui, China.
School of Pharmacy, Bengbu Medical College, No.2600, Donghai Avenue, Bengbu 233000, Anhui, China; Department of Rheumatology and Immunology, the First Affiliated Hospital to Bengbu Medical College, Bengbu 233000, Anhui, China.
Eur J Pharmacol. 2019 Jun 5;852:179-188. doi: 10.1016/j.ejphar.2019.02.036. Epub 2019 Feb 20.
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-α, interleukin-1β, and interleukin-6), increasing the levels of M2 cytokines (interleukin-10 and transforming growth factor-β1), increasing the expression of arginase 1(Arg1) (M2 marker) and decreasing the expression of inducible nitric oxide synthase (iNOS) (M1 marker). BBR also downregulated the ratio of Th17/Treg cells. Further research on the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/nuclear factor κB (NF-κB) 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-IκBα) 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-кB pathway.
小檗碱（BBR）是一种具有优异抗炎特性的传统民间药物。本研究旨在探讨 BBR 在大鼠佐剂性关节炎（AA）中的抗关节炎作用及其对巨噬细胞极化的调节作用。大鼠用完全弗氏佐剂（CFA）免疫，然后给予 BBR（40、80、160mg/kg）口服 14 天。BBR 显著减轻爪肿胀和关节炎总体评估，缓解关节破坏和炎症细胞浸润。BBR 还显著降低了胸腺指数和胸腺细胞增殖。此外，BBR 治疗通过降低 M1 细胞因子（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）水平、增加 M2 细胞因子（白细胞介素-10 和转化生长因子-β1）水平、增加精氨酸酶 1（M2 标志物）的表达和降低诱导型一氧化氮合酶（iNOS）（M1 标志物）的表达来抑制巨噬细胞的吞噬功能，并恢复 M1/M2 的平衡。BBR 还下调了 Th17/Treg 细胞的比例。进一步研究 5'-单磷酸腺苷（AMP）激活蛋白激酶（AMPK）/核因子κB（NF-κB）通路发现，BBR 上调了 AMPK 的活性，同时下调了磷酸化 RelA（p-p65）、磷酸化 NF-κB 抑制剂α（p-IκBα）和环氧化酶（COX）-2 的表达。因此，我们的研究结果表明，BBR 通过调节 AMPK/NF-κB 通路调节巨噬细胞极化，对 AA 大鼠具有显著的治疗作用。
