title: Alpha-mangostin from mangosteen (Garcinia mangostana Linn.)pericarp extract reduces high fat-diet induced hepatic steatosis in rats by regulating mitochondria function and apoptosis.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is caused by multiple factors including hepatic oxidative stress, lipotoxicity, and mitochondrial dysfunction. Obesity is among the risk factors for NAFLD alongside type 2 diabetes mellitus and hyperlipidemia. α- mangostin (α-MG) extracts from the pericarps of mangosteen (Garcinia mangostana Linn.)may regulate high fat diet-induced hepatic steatosis; however the underlying mechanisms remain unknown. The aim of this study was to investigate the regulatory effect of α-MG on high fat diet-induced hepatic steatosis and the underlying mechanisms related to mitochondrial functionality and apoptosis in vivo and in vitro.
  
  
  METHODS
  Sprague Dawley (SD) rats were fed on either AIM 93-M control diet, a high-fat diet (HFD), or high-fat diet supplemented with 25 mg/day mangosteen pericarp extract (MGE) for 11 weeks. Thereafter, the following were determined: body weight change, plasma free fatty acids, liver triglyceride content, antioxidant enzymes (superoxide dismutase, SOD; glutathione, GSH; glutathione peroxidase, GPx; glutathione reductase GRd; catalase, CAT) and mitochondrial complex enzyme activities. In the in vitro study, primary liver cells were treated with 1 mM free fatty acid (FFA) (palmitate: oleate acid = 2:0.25) to induce steatosis. Thereafter, the effects of α-MG (10 μM, 20 μM, 30 μM) on total and mitochondria ROS (tROS, mitoROS), mitochondria bioenergetic functions, and mitochondrial pathway of apoptosis were examined in the FFA-treated primary liver cells.
  
  
  RESULTS
  The MGE group showed significantly decreased plasma free fatty acids and hepatic triglycerides (TG) and thiorbarbituric acid reactive substances (TBARS) levels; increased activities of antioxidant enzymes (SOD, GSH, GPx, GRd, CAT); and enhanced NADH-cytochromecreductase (NCCR) and succinate-cytochromecreductase (SCCR) activities in the liver tissue compared with HFD group. In the in vitro study, α-MG significantly increased mitochondrial membrane potential, enhanced cellular oxygen consumption rate (OCR), decreased tROS (total ROS) and mitoROS (mitochondrial ROS) levels ; reduced Ca2+and cytochromec(cytc) release from mitochondria, and reduced caspases 9 and 3 activities compared with control group.
  
  
  CONCLUSIONS
  These findings demonstrate α-MG attenuated hepatic steatosis in high fat-diet fed rats potentially through enhanced cellular antioxidant capacity and improved mitochondrial functions as well as suppressed apoptosis of hepatocytes. The findings of study represent a novel nutritional approach on the use of α-MG in the prevention and management of NAFLD.
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan.
authors.forename: Shin-Yu
authors.initials: SY
authors.lastname: Tsai
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan.
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Chung
authors.affiliation: Institute of Food Bioresources and Technology, Dedan Kimathi University of Technology, P.O. Box 657-10100 Nyeri, Kenya.
authors.forename: Eddy E
authors.initials: EE
authors.lastname: Owaga
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan.
authors.forename: I-Jong
authors.initials: IJ
authors.lastname: Tsai
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan.
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Yuan Lyu Technology Corporation, 10F-3, 120 Chung Cheng 1st Road, Kaohsiung, 802 Taiwan.
authors.forename: Jeng-I
authors.initials: JI
authors.lastname: Tsai
authors.affiliation: Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, 112 Taiwan.
authors.forename: Tien-Shun
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan.
authors.forename: Rong-Hong
authors.initials: RH
authors.lastname: Hsieh
keywords: Antioxidant enzymes; Fat infiltration; Mitochondria dysfunction; Mitochondrial pathway apoptosis; α-mangostin