Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling.
Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling.
复制标题
去亚甲基小檗碱通过调节 NF-B 信号传导预防小鼠肝纤维化
DOI：
10.3390/ijms17071036
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发表时间：
2016-06-30
影响因子：
5.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Wang Y;Zhao Z;Yan Y;Qiang X;Zhou C;Li R;Chen H;Zhang Y
去甲基小檗碱(DMB)是黄连素(BBR)在体内的重要代谢物。最近的报道揭示了BBR的多种新的治疗应用。然而，DMB的药理活性仍有待阐明。本研究旨在证实DMB在体内外的保肝、抗肝纤维化作用。在这里，我们证明了DMB对硫代乙酰胺(TAA)诱导的小鼠肝纤维化具有保护作用，并且与BBR相比显示出更高的安全性。流式细胞仪和Western blotting分析表明，DMB能抑制肝星状细胞(HSC)的激活，并通过核因子-κB(NF-κB)级联反应诱导细胞凋亡。免疫组织化学和定量聚合酶链式反应分析表明，DMB对胶原合成也有抑制作用，并可通过阻断转化生长因子β1-Smad信号通路，减少基质金属蛋白酶及其组织抑制物(TIMPs)的表达，增加胶原降解。这些发现表明DMB有可能通过抑制HSC的激活来减轻肝纤维化。
Demethyleneberberine (DMB) is an essential metabolite of Berberine (BBR) in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA)-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs) and induce cell apoptosis through the nuclear factor-κB (NF-κB) cascade. Immunohistochemical (IHC) and quantitative polymerase chain reaction (qPCR) analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor β 1 (TGF-β1)-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs). These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation.