9-O-benzoyl-substituted berberine exerts a triglyceride-lowering effect through AMPK signaling pathway in human hepatoma HepG2 cells
9-O-benzoyl-substituted berberine exerts a triglyceride-lowering effect through AMPK signaling pathway in human hepatoma HepG2 cells
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9-O-苯甲酰基取代小檗碱通过 AMPK 信号通路在人肝癌 HepG2 细胞中发挥降低甘油三酯的作用
DOI：
10.1016/j.etap.2018.09.007
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发表时间：
2018-12-01
影响因子：
4.3
通讯作者：
Kang, Ning
中科院分区：
文献类型：
--
作者：
Cao, Shijie;Yu, Shengyang;Kang, Ning
小檗碱是从黄连中提取的一种异喹啉类生物碱，在体内外均具有降血脂作用。我们以前发现，小檗碱可以通过激活AMP激活蛋白激酶（AMPK），脂质代谢的主要调节剂，降低人肝癌HepG 2细胞内甘油三酯含量。为了寻找更有效的药物，我们分离并合成了几种小檗碱类似物（A1-A13），并在HepG 2细胞中研究了它们的降胆固醇作用及其可能的机制。在这些小檗碱类似物中，9-O-苯甲酰基取代的小檗碱（A13）显示出与AMPK的强亲和力，并显著上调磷酸化Thr 172 AMPK α亚基的水平。同时，A13降低细胞甘油三酯水平。此外，A13还可介导AMPK信号通路中参与甘油三酯合成和脂肪酸氧化的下游蛋白的mRNA水平。提示A13可能通过激活AMPK通路发挥降血脂作用，从而调节高脂血症。
Berberine is an isoquinoline alkaloid extracted from Rhizoma coptidis and shows anti-hyperlipidemia effect in vivo and in vitro. We previously found that berberine could decrease the intracellular triglyceride content in human hepatoma HepG2 cells through activation of AMP-activated protein kinase (AMPK), a major regulator of lipid metabolism. Herein, to find a more effective agent, several berberine analogues (A1-A13) were isolated and synthesized, and the triglyceride-lowering effects and potential mechanisms were investigated in HepG2 cells. Among these berberine analogues, 9-O-benzoyl-substituted berberine (A13) showed strong affinity to AMPK and significantly up-regulated the levels of phospho-Thr172 AMPK alpha subunit. Meanwhile, A13 reduced the cellular triglyceride levels. Furthermore, A13 could mediate the mRNA levels of downstream proteins involved in triglyceride synthesis and fatty acid oxidation of AMPK signaling pathway. These results suggested that A13 exerts a triglyceride-lowering effect via stimulation of AMPK pathway, which may be beneficial to regulate hyperlipidemia.