Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats  

作　　者：Zhen-li Su Peng-zhou Hang Juan Hu Yu-yang Zheng Han-qi Sun Jing Guo Ke-yu Liu Zhi-min Du 

机构地区：[1]Institute of Clinical Pharmacology,The Second Affiliated Hospital of Harbin Medical University(University Key Laboratory of Drug Research,Heilongjiang Province),Harbin 150086,China [2]Department of Clinical Pharmacology,College of Pharmacy,Harbin Medical University,Harbin 150081,China [3]State Key Laboratory of Quality Research in Chinese Medicines,Macao University of Science and Technology,Macao 999078,China

出　　处：《Acta Pharmacologica Sinica》2020年第8期1085-1092,共8页中国药理学报（英文版）

基　　金：the Major Program of the National Natural Science Foundation of China(81230081);the Translational Fund of the Sino-Russian Medical Research Center,Heilongjiang Academy of Medical Sciences(CR201814).

摘　　要：Hyperlipidemia(HPL)characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases.Proprotein convertase subtilsin/kexin type 9(PCSK9)is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor(LDLR)in the lysosome of hepatocytes.Aloe-emodin(AE)is one of potentially bioactive components of Chinese traditionalmedicine Daming capsule.In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models.High-fat diet-induced rats were treated with AE(100 mg/kg per day,ig)for 6 weeks.We found that AE administration significantly decreased the levels of total cholesterol(TC)and LDL in the serum and liver tissues.Moreover,AE administration ameliorated HPL-induced hepaticlipid aggregation.But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats.A cellular model of HPL was established in human hepatoma(HepG2)cells treated with cholesterol(20 μg/mL)and 25-hydroxycholesterol(2 μg/mL),which exhibited markedly elevated cholesterol levels.The increased cholesterol levels could be reversed by subsequent treatment with AE(30 μM).In both the in vivo and in vitro HPL models,we revealed that AE selectively suppressed the stero-regulatory element-binding protein-2(SREBP-2)and hepatocyte nuclear factor(HNF)1α-mediated PCSK9 signaling,which in turn upregulated LDL receptor(LDLR)and promoted LDL uptake.This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

关 键 词：ALOE-EMODIN HYPERLIPIDEMIA CHOLESTEROL PCSK9 LDL receptor HepG2 cells ATORVASTATIN 

分 类 号：R285.5[医药卫生—中药学]