Zi Lin1, Zheng-Feng Wu1, Cui-Hua Jiang2, Qing-Wen Zhang3, Sheng Ouyang4, Chun-Tao Che5, Jian Zhang6, Zhi-Qi Yin7. 1. Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China. 2. Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China; Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China. 3. State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao. 4. Department of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang 330004, PR China; Department of Medicinal Chemistry and Pharmacognosy, and WHO Collaborating Center for Tradition Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. 5. Department of Medicinal Chemistry and Pharmacognosy, and WHO Collaborating Center for Tradition Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. 6. Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China. 7. Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, China; Department of Medicinal Chemistry and Pharmacognosy, and WHO Collaborating Center for Tradition Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: cpu-yzq@cpu.edu.cn.
Abstract
BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism. STUDY DESIGN: Sprague Dawley rats were fed with high-fat diet (HFD) for 6 weeks to induce HS and treated with or without ChE by gavage for 4 weeks. METHODS: The body weight, relative liver weight and liver fat content were measured. Serum and liver total cholesterol, triglyceride and non-esterified fatty acids, as well as hepatic malonaldehyde levels were accessed by biochemical methods. Serum and liver TNF-α levels were quantified by ELISA kit. Histologic analysis and 1H-MRS study were performed to evaluate HS level. RT-PCR and Western blot were also applied to observe the expression changes of key factors involved in hepatic lipid intake, synthesis, utilization and export. RESULTS: ChE significantly decreased the rats' body weight, serum lipid and TNF-α level. ChE also reduced their relative liver weight, liver fat content, hepatic oxidative products and TNF-α level. Hepatic steatosis in HFD-fed rats was effectively regressed after 2-weeks administration of ChE. Moreover, ChE treatment remarkably reduced HFD-induced high expression level of fatty acid synthesis genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1 and fatty acid synthase). However, it had no effect on mRNA expression of some genes involved in lipid uptake, β-oxidation and lipid outflow. CONCLUSION: ChE exerted a promising regression effect on HS due to a reduced level of serum non-esterified fatty acids which might lead to a decrease in the amount of lipid taken in by the liver, as well as owing to the inhibition of hepatic lipid de novo synthesis to reduce liver lipid production.
BACKGROUND:Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism. STUDY DESIGN:Sprague Dawley rats were fed with high-fat diet (HFD) for 6 weeks to induce HS and treated with or without ChE by gavage for 4 weeks. METHODS: The body weight, relative liver weight and liver fat content were measured. Serum and liver total cholesterol, triglyceride and non-esterified fatty acids, as well as hepatic malonaldehyde levels were accessed by biochemical methods. Serum and liver TNF-α levels were quantified by ELISA kit. Histologic analysis and 1H-MRS study were performed to evaluate HS level. RT-PCR and Western blot were also applied to observe the expression changes of key factors involved in hepatic lipid intake, synthesis, utilization and export. RESULTS:ChE significantly decreased the rats' body weight, serum lipid and TNF-α level. ChE also reduced their relative liver weight, liver fat content, hepatic oxidative products and TNF-α level. Hepatic steatosis in HFD-fed rats was effectively regressed after 2-weeks administration of ChE. Moreover, ChE treatment remarkably reduced HFD-induced high expression level of fatty acid synthesis genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1 and fatty acid synthase). However, it had no effect on mRNA expression of some genes involved in lipid uptake, β-oxidation and lipid outflow. CONCLUSION:ChE exerted a promising regression effect on HS due to a reduced level of serum non-esterified fatty acids which might lead to a decrease in the amount of lipid taken in by the liver, as well as owing to the inhibition of hepatic lipid de novo synthesis to reduce liver lipid production.