The Safety and Anti-Hypercholesterolemic Effect of Coptisine in Syrian Golden Hamsters
The Safety and Anti-Hypercholesterolemic Effect of Coptisine in Syrian Golden Hamsters
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DOI：
10.1007/s11745-014-3983-7
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发表时间：
2015-02-01
期刊：
影响因子：
1.9
通讯作者：
Li, Xuegang
中科院分区：
文献类型：
--
作者：
He, Kai;Ye, Xiaoli;Li, Xuegang
本研究以叙利亚金黄地鼠为实验动物，观察黄连碱的降胆固醇作用。安全性试验结果表明黄连碱是一种安全、低毒的化合物。黄连碱对高脂高胆固醇饮食（HFHC）引起的血脂异常水平具有有益作用：浓度为70.05 mg/kg时，黄连碱显著导致总胆固醇、甘油三酯和低密度脂蛋白胆固醇（LDL-c）水平分别降低26.70%、15.38%和22.22%，血清高密度脂蛋白胆固醇（HDL-c）升高41.74%（p < 0.01）。此外，黄连碱给药后，仓鼠粪便中总胆汁酸（TBA）水平升高。进一步的研究表明，高剂量黄连碱可下调仓鼠肝脏3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的mRNA和蛋白表达（p < 0.05），显著上调低密度脂蛋白受体（LDLR）和胆固醇7 α-羟化酶（CYP 7A 1）的mRNA和蛋白表达。在黄连碱处理的动物中，顶端钠依赖性胆盐转运蛋白表达下调，但与HFHC组无显著差异。综上所述，我们的结果表明，高剂量的黄连碱可以通过抑制HMGCR的表达来抑制胆固醇合成，并通过上调LDLR和CYP 7A 1的表达来促进胆固醇的利用和排泄。这些发现表明黄连碱在抗高胆固醇血症中的关键作用，因此需要考虑将其作为潜在的天然降胆固醇剂。
Current work was conducted to evaluate the cholesterol-lowering effect of coptisine extracted from Rhizoma coptidis in Syrian golden hamsters. The safety results indicated that coptisine was a safe and low-toxic compound. Coptisine showed a beneficial effect in the abnormal serum lipid levels induced by a high-fat and high-cholesterol diet (HFHC): at a concentration of 70.05 mg/kg, coptisine significantly led to a decrease in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-c) levels by 26.70, 15.38, and 22.22 %, respectively, and high-density lipoprotein cholesterol (HDL-c) was increased by 41.74 % in serum of hamsters (p < 0.01). In addition, total bile acid (TBA) levels in feces of hamsters were elevated after coptisine administration. Further investigation has suggested that the mRNA and protein expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) in the liver of hamsters was down-regulated by high-dosage coptisine treatment (p < 0.05); mRNA and protein expression of low-density lipoprotein receptor (LDLR) and cholesterol 7 alpha-hydroxylase (CYP7A1) were dramatically up-regulated by coptisine administration. The apical sodium-dependent bile salt transporter expression was down-regulated in the coptisine-treated animals, but showed no significant differences from the HFHC groups. Taken together, our results demonstrate that a high dosage of coptisine could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. These findings suggest a critical role for coptisine in anti- hypercholesterolemia, and thus it needs to be considered as a potential natural cholesterol lowering agent.