PMID- 27980597 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220331 IS - 1743-7075 (Print) IS - 1743-7075 (Electronic) IS - 1743-7075 (Linking) VI - 13 DP - 2016 TI - Alpha-mangostin from mangosteen (Garcinia mangostana Linn.) pericarp extract reduces high fat-diet induced hepatic steatosis in rats by regulating mitochondria function and apoptosis. PG - 88 LID - 88 AB - 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. alpha- mangostin (alpha-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 alpha-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 alpha-MG (10 muM, 20 muM, 30 muM) 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-cytochrome c reductase (NCCR) and succinate-cytochrome c reductase (SCCR) activities in the liver tissue compared with HFD group. In the in vitro study, alpha-MG significantly increased mitochondrial membrane potential, enhanced cellular oxygen consumption rate (OCR), decreased tROS (total ROS) and mitoROS (mitochondrial ROS) levels ; reduced Ca(2+) and cytochrome c (cyt c) release from mitochondria, and reduced caspases 9 and 3 activities compared with control group. CONCLUSION: These findings demonstrate alpha-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 alpha-MG in the prevention and management of NAFLD. FAU - Tsai, Shin-Yu AU - Tsai SY AD - School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan. FAU - Chung, Pei-Chin AU - Chung PC AD - School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan. FAU - Owaga, Eddy E AU - Owaga EE AD - Institute of Food Bioresources and Technology, Dedan Kimathi University of Technology, P.O. Box 657-10100 Nyeri, Kenya. FAU - Tsai, I-Jong AU - Tsai IJ AD - School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan. FAU - Wang, Pei-Yuan AU - Wang PY AD - School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan. FAU - Tsai, Jeng-I AU - Tsai JI AD - Yuan Lyu Technology Corporation, 10F-3, 120 Chung Cheng 1st Road, Kaohsiung, 802 Taiwan. FAU - Yeh, Tien-Shun AU - Yeh TS AD - Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, 112 Taiwan. FAU - Hsieh, Rong-Hong AU - Hsieh RH AD - School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110 Taiwan. LA - eng PT - Journal Article DEP - 20161201 PL - England TA - Nutr Metab (Lond) JT - Nutrition & metabolism JID - 101231644 PMC - PMC5134003 OTO - NOTNLM OT - Antioxidant enzymes OT - Fat infiltration OT - Mitochondria dysfunction OT - Mitochondrial pathway apoptosis OT - alpha-mangostin EDAT- 2016/12/17 06:00 MHDA- 2016/12/17 06:01 PMCR- 2016/12/01 CRDT- 2016/12/17 06:00 PHST- 2016/07/25 00:00 [received] PHST- 2016/11/22 00:00 [accepted] PHST- 2016/12/17 06:00 [entrez] PHST- 2016/12/17 06:00 [pubmed] PHST- 2016/12/17 06:01 [medline] PHST- 2016/12/01 00:00 [pmc-release] AID - 148 [pii] AID - 10.1186/s12986-016-0148-0 [doi] PST - epublish SO - Nutr Metab (Lond). 2016 Dec 1;13:88. doi: 10.1186/s12986-016-0148-0. eCollection 2016.