Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing 210029, PR China; School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Int Immunopharmacol. 2018 Apr;57:121-131. doi: 10.1016/j.intimp.2018.01.049. Epub 2018 Feb 24.
Berberine has been reported to have protective effects in colitis treatment. However, the detailed mechanisms remain unclear. Herein, we demonstrated that berberine could protect against dextran sulfate sodium (DSS)-induced colitis in mice by regulating macrophage polarization. In the colitis mouse model, berberine ameliorated DSS-induced colon shortening and colon tissue injury. Moreover, berberine-treated mice showed significant reduction in the disease activity index (DAI), pro-inflammatory cytokines expression and macrophages infiltration compared with the DSS-treated mice. Notably, berberine significantly reduced the percentage of M1 macrophages. In vitro analysis also confirmed the inhibitory effects of berberine on macrophages M1 polarization in RAW267.4 cells. Further investigation showed that berberine promoted AKT1 expression in mRNA and protein level. Silence of AKT1 abolished the inhibitory effect of berberine on macrophages M1 polarization. The berberine-induced AKT1 expression promoted suppressers of cytokine signaling (SOCS1) activation, which inhibited nuclear factor-kappa B (NF-κB) phosphorylation. In addition, we also found that berberine activated AKT1/SOCS1 signaling pathway but inhibited p65 phosphorylation in macrophages in vivo. Therefore, we concluded that berberine played a regulatory role in macrophages M1 polarization in DSS-induced colitis via AKT1/SOCS1/NF-κB signaling pathway. This unexpected property of berberine may provide a potential explanation for its protective effects in colitis treatment.
小檗碱被报道具有治疗结肠炎的保护作用。然而，其详细机制尚不清楚。在此，我们证明小檗碱可以通过调节巨噬细胞极化来保护葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠。在结肠炎小鼠模型中，小檗碱改善了 DSS 诱导的结肠缩短和结肠组织损伤。此外，与 DSS 处理的小鼠相比，小檗碱处理的小鼠疾病活动指数（DAI）、促炎细胞因子表达和巨噬细胞浸润显著降低。值得注意的是，小檗碱显著降低了 M1 巨噬细胞的比例。体外分析也证实了小檗碱对 RAW267.4 细胞中巨噬细胞 M1 极化的抑制作用。进一步研究表明，小檗碱促进 AKT1 在 mRNA 和蛋白水平的表达。AKT1 沉默消除了小檗碱对巨噬细胞 M1 极化的抑制作用。小檗碱诱导的 AKT1 表达促进了细胞因子信号转导抑制物（SOCS1）的激活，从而抑制了核因子-κB（NF-κB）的磷酸化。此外，我们还发现小檗碱在体内激活了 AKT1/SOCS1 信号通路，但抑制了巨噬细胞中 p65 的磷酸化。因此，我们得出结论，小檗碱通过 AKT1/SOCS1/NF-κB 信号通路在 DSS 诱导的结肠炎中对巨噬细胞 M1 极化发挥调节作用。小檗碱的这种意想不到的特性可能为其在结肠炎治疗中的保护作用提供了潜在的解释。
