13-Methylberberine, a berberine analogue with stronger anti-adipogenic effects on mouse 3T3-L1 cells.
13-Methylberberine, a berberine analogue with stronger anti-adipogenic effects on mouse 3T3-L1 cells.
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DOI：
10.1038/srep38129
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发表时间：
2016-12-05
影响因子：
4.6
通讯作者：
Sato F
中科院分区：
文献类型：
--
作者：
Chow YL;Sogame M;Sato F
脂类代谢调节是代谢综合征研究的一个主要焦点，在这个领域中，许多天然和合成的化学物质正在不断地进行体外和体内活性的筛选。黄连素是一种苄基异喹啉类植物生物碱，因其抗肥胖作用以及作为潜在的降胆固醇和降甘油三酯药物而被广泛研究。我们筛选了11种原黄连素和2种苯并菲并菲生物碱对3T3-L1脂肪细胞的抗成脂作用，发现13-甲基黄连素的活性最强。13-甲基黄连素下调主要脂肪细胞分化转录因子--过氧化物酶体增殖物激活受体γ和CCAAT增强子结合蛋白α(C/EBpα)及其靶基因的表达。PPARγ、C/EBPα和固醇调节元件结合蛋白1的蛋白水平降低，这种降脂作用可被AMP激活的蛋白激酶抑制剂减弱，这表明该化合物的作用需要AMPK信号通路。Akt磷酸化减少意味着从头合成脂质减少。黄连素的C-13甲基取代增加了其在处理细胞中的积累量，表明13-甲基黄连素比黄连素有更好的吸收和更高的积累量。我们的发现表明，13-甲基黄连素具有作为一种减肥药物的潜力。
Lipid metabolism modulation is a main focus of metabolic syndrome research, an area in which many natural and synthetic chemicals are constantly being screened for in vitro and in vivo activity. Berberine, a benzylisoquinoline plant alkaloid, has been extensively investigated for its anti-obesity effects and as a potential cholesterol and triglyceride-lowering drug. We screened 11 protoberberine and 2 benzophenanthridine alkaloids for their anti-adipogenic effects on 3T3-L1 adipocytes and found that 13-methylberberine exhibited the most potent activity. 13-Methylberberine down-regulated the expression of the main adipocyte differentiation transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα), as well as their target genes. PPARγ, C/EBPα, and sterol regulatory element binding protein 1 (SREBP-1) protein levels were reduced, and this lipid-reducing effect was attenuated by an AMP-activated protein kinase (AMPK) inhibitor, indicating that the effect of this compound requires the AMPK signaling pathway. Decreased Akt phosphorylation suggested reduced de novo lipid synthesis. C-13 methyl substitution of berberine increased its accumulation in treated cells, suggesting that 13-methylberberine has improved absorption and higher accumulation compared to berberine. Our findings suggest that 13-methylberberine has potential as an anti-obesity drug.
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影响因子：
5.1
作者：
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