Xi Youli, Wu Miaozong, Li Hongxia, Dong Siqi, Luo Erfei, Gu Mingbo, Shen Xiao, Jiang Yabo, Liu Yaqun, Liu Hua
Department of Pharmacology, Medical School, Southeast University, Nanjing, Jiangsu, China.
Cell Physiol Biochem. 2015;35(6):2349-59. doi: 10.1159/000374037. Epub 2015 Apr 15.
BACKGROUND/AIMS: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms.
High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca(2+)/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated.
Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway.
These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.
背景/目的：肥胖相关脂肪性肝病影响着数百万人。本研究旨在评估黄芩苷对高脂饮食诱导的肥胖小鼠治疗肥胖和脂肪肝的效果，并研究其潜在的分子机制。
用不同剂量的黄芩苷（100、200和400mg/kg/d）治疗高脂饮食诱导的肥胖动物。称量全身、脂肪垫和肝脏的重量。进一步评估高脂血症、肝脏脂肪变性、肝功能以及肝脏钙/钙调蛋白依赖性蛋白激酶激酶β（CaMKKβ）/AMP激活的蛋白激酶（AMPK）/乙酰辅酶A羧化酶（ACC）。
黄芩苷显著降低了高脂饮食喂养小鼠的肝脏、附睾脂肪和体重，这与血清甘油三酯、总胆固醇、低密度脂蛋白、丙氨酸转氨酶和天冬氨酸转氨酶水平降低有关，但血清高密度脂蛋白水平升高。病理分析显示，黄芩苷剂量依赖性地降低了肝脏脂肪变性程度，低剂量时主要减少大泡性脂肪变性，而高剂量黄芩苷时大泡性和小泡性脂肪变性均减少。黄芩苷剂量依赖性地抑制肝脏CaMKKβ/AMPK/ACC信号通路。
这些数据表明，高达400mg/kg/d的黄芩苷是安全的，并且能够降低肥胖和脂肪肝疾病的程度。肝脏CaMKKβ/AMPK/ACC信号通路可能介导黄芩苷在高脂饮食动物模型中的治疗作用。
