title: Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non-alcoholic fatty liver disease model.
abstract: BACKGROUND
  Ilex latifolia Thunb. (Da Ye Dong Qing) is used for weight loss and for its antidiabetic effects. This study aims to investigate the beneficial effects and potential mechanisms of action of crude triterpenoid saponins (CTS) from I. latifolia in a mouse model of high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Male C57BL/6 mice (n = 50), were arbitrarily divided into five groups (n = 10 in each group): a control group, HFD group, simvastatin group (10 mg/kg/day), and two CTS treatment groups (100 and 200 mg/kg/day). All mice except those in the control group were fed an HFD for 4 weeks. Animals in the treatment groups were orally administered simvastatin or CTS for 8 weeks. Oral glucose tolerance tests and insulin tolerance tests were performed. At the end of treatment, plasma lipid levels, and oxidative parameters in the liver were measured using commercial test kits. Western blotting was used to evaluate whether CTS induced AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase activation, and the expression of transcription factors and their target genes was evaluated in a quantitative PCR assay.
  
  
  RESULTS
  Compared with the HFD group, the CTS (200 mg/kg/day) treatment group showed significantly decreased plasma lipid parameters (P < 0.001, P = 0.018, and P = 0.005 for triglycerides, total cholesterol and low-density lipoprotein cholesterol, respectively), and improved insulin resistance (P = 0.006). CTS (100 and 200 mg/kg/day) supplementation also reduced hepatic lipids and protected the liver from oxidative stress by attenuating malondialdehyde content (P < 0.001 and P < 0.001, respectively) and restoring aspartate aminotransferase levels (P < 0.001 and P < 0.001, respectively). Moreover, CTS (200 mg/kg/day) reduced lipid accumulation by enhancing AMPK phosphorylation and inhibiting expression of sterol regulatory element-binding proteins (SREBPs) and their target genes SREBP-1c, SREBP-2, fatty acid synthase, and stearoyl-CoA desaturase (P = 0.013, P = 0.007, P = 0.011, and P = 0.014, respectively).
  
  
  CONCLUSIONS
  CTS from I. latifolia improved insulin resistance and liver injury in HFD-fed mice, and attenuated NAFLD via the activation of AMPK and inhibition of the gene expression of SREBPs and some of their target molecules.
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Rui-Bing
authors: RB
authors: Feng
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Chun-Lin
authors: CL
authors: Fan
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Qing
authors: Q
authors: Liu
authors: Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Zhong
authors: Z
authors: Liu
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Wei
authors: W
authors: Zhang
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Yao-Lan
authors: YL
authors: Li
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Wei
authors: W
authors: Tang
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Ying
authors: Y
authors: Wang
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Man-Mei
authors: MM
authors: Li
authors: College of Pharmacy, Jinan University, Guangzhou, 510632 People's Republic of China.|Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632 People's Republic of China.
authors: Wen-Cai
authors: WC
authors: Ye