Author/Authors :
Han, Bing School of Life Sciences - Southwest University, Chongqing, 400715, China , Kou, Shuming School of Life Sciences - Southwest University, Chongqing, 400715, China , He, Kai School of Pharmaceutical Sciences - Southwest University, Chongqing, 400715, China , Han, Yulong School of Life Sciences - Southwest University, Chongqing, 400715, China , Wang, Yue School of Life Sciences - Southwest University, Chongqing, 400715, China , Huang, Tao School of Pharmaceutical Sciences - Southwest University, Chongqing, 400715, China , Zhou, Xia School of Pharmaceutical Sciences - Southwest University, Chongqing, 400715, China , Xiao, Yubo School of Pharmaceutical Sciences - Southwest University, Chongqing, 400715, China , Li, Xuegang School of Pharmaceutical Sciences - Southwest University, Chongqing, 400715, China , Ye, Xiaoli School of Life Sciences - Southwest University, Chongqing, 400715, China
Abstract :
The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis
(RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol
(HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell
death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently
labeled cholesterol in caudal artery was reduced dose-dependently after BBM treatment.
For adult zebrafish, administration of 0.2% BBM exhibited a significant decrease in plasma
total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c)
levels by 37%, 38% and 28%, respectively, along with a fall in lipid content in liver. Further
investigation suggested that the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A
reductase (HMGCR) and microsomal triglyceride transfer protein (MTP) in liver were downregulated
and the transcription levels of liver gene low-density lipoprotein receptor (LDLR)
and cytochrome P450 polypeptide 1a of subfamily A of family 7 (CYP7A1a) were significantly
up-regulated with BBM treatment. Histological study showed that BBM can alleviate hepatic
steatosis induced by HC diet. These data suggested that BBM has anti-hypercholesterolemic and
hepatoprotective effects. The mechanism probably related to the up-regulation of cholesterol
transport and bile acid synthesis as well as inhibition of cholesterol synthesis and lipoprotein
assembly or secretion.
Keywords :
Vascular lipid accumulation , Hypercholesterolemia , Zebrafish , Rhizoma Coptidis , Berbamine