Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Department of Health Industry Technology Management, Chung Shan Medical University, Taichung 40201, Taiwan.
Int J Mol Sci. 2021 Dec 6;22(23):13163. doi: 10.3390/ijms222313163.
Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid β-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5' adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.
新绿原酸（5-咖啡酰奎尼酸；5-CQA）是从桑叶中分离得到的主要酚类化合物，具有抗氧化和抗炎作用。虽然它可以调节脂质代谢，但分子机制尚不清楚。我们使用非酒精性脂肪性肝病（NAFLD）的体外模型，即在 HepG2 细胞中用油酸（OA）诱导脂质积累，评估了 5-CQA 的缓解作用。我们观察到 5-CQA 通过下调固醇调节元件结合蛋白 1（SREBP1）和脂肪酸合酶（FASN）的表达来改善 OA 诱导的细胞内脂质积累，从而调节脂肪酸的合成，以及 SREBP2 和 HMG-CoA 还原酶（HMG-CoR）的表达，调节胆固醇的合成。5-CQA 的治疗还增加了脂肪酸β氧化酶的表达。值得注意的是，5-CQA 减弱了 OA 诱导的 miR-34a 表达。用 miR-34a 模拟物或 miR-34a 抑制剂进行转染实验表明，miR-34a 抑制了 Sirtuin 1（SIRT1）的表达并使 5'腺苷一磷酸激活蛋白激酶（AMPK）失活。我们的结果表明，5-CQA 通过下调 miR-34a 缓解脂质积累，从而激活 SIRT1/AMPK 通路。
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