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

BackgroundNon-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.MethodsSprague 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.ResultsThe 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, 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 cytochrome c (cyt c) release from mitochondria, and reduced caspases 9 and 3 activities compared with control group.ConclusionThese 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.

Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats

“…We speculated that a decrease in MDA was due to the scavenging of free radicals by MPP compounds, and to promoting activities of antioxidant enzymes in prostate tissues. In a previous study, mangosteen pericarp extract supplementation for 11 weeks produced significantly decreased plasma MDA levels and increased activities of superoxide dismutase (SOD), GPx, GRd, and CAT in rats fed an HFD 37 . Fang et al 38 demonstrated that α-mangostin treatment resulted in increases in SOD and GPx activities and the GSH content of the retina both in vivo and in vitro.…”

Mangosteen Vinegar Rind from Garcinia mangostana Prevents High‐Fat Diet and Streptozotocin‐Induced Type II Diabetes Nephropathy and Apoptosis

“…Taher and his group found that administration of ethanolic extract of G. mangostana pericarp to normoglycaemic and STZ‐induced diabetic rats significantly ameliorated blood glucose level, lipid profile, plasma lipid and kidney function parameters, and hepatic histological alterations; possibly via increasing the number of insulin‐producing β‐cells (Taher et al., ). Tsai and team observed that α‐mangostin (from mangosteen pericarp) treatment for 11 weeks significantly reduced HFD‐induced hepatopathy through enhancing cellular antioxidant capacity, improving mitochondrial functions, and suppressing hepatocytes apoptosis (Tsai et al., ). It suggests that α‐mangostin contained MVR, which may reduce the renal apoptosis through improving mitochondrial integrity and diminishing oxidative stress.…”

Cytotoxicity and antioxidant activity of plant extracts from Vietnam

“…M. indica ở nồng độ IC10 đã kích thích tạo gốc iROS sau khi xử lý thêm với TBH và làm tăng lượng iROS khoảng 20%, trong khi G. mangostana và T. catappa lại làm giảm iROS (số liệu không trình bày). Phát hiện này cũng được thông báo trong một số nghiên cứu trước đây (Tsai et al, 2016;Moongkarndi et al, 2004;Huang et al, 2018). Sự ức chế iROS của G.mangostana và T. catappa khác biệt đáng kể ở nồng độ sử dụng IC25 và IC50.…”