Garcinia cambogia Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation.

Joo-Hui Han,Min-Ho Park,Chang-Seon Myung

doi:10.3390/antiox10081226

Joo-Hui Han, Min-Ho Park + Show 1 more

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https://doi.org/10.3390/antiox10081226

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Journal: Antioxidants	Publication Date: Jul 29, 2021
Citations: 17	License type: CC BY 4.0

Affiliation: Chungnam National University

Abstract

Excessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. Garcinia cambogia (G. cambogia) is used as an anti-obesity supplement, and its protective potential against NAFLD has been investigated. This study aims to present the therapeutic effects of G. cambogia on NAFLD and reveal underlying mechanisms. High-fat diet (HFD)-fed mice were administered G. cambogia for eight weeks, and steatosis, apoptosis, and biochemical parameters were examined in vivo. FFA-induced HepG2 cells were treated with G. cambogia, and lipid accumulation, apoptosis, ROS level, and signal alterations were examined. The results showed that G. cambogia inhibited HFD-induced steatosis and apoptosis and abrogated abnormalities in serum chemistry. G. cambogia increased in NRF2 nuclear expression and activated antioxidant responsive element (ARE), causing induction of antioxidant gene expression. NRF2 activation inhibited FFA-induced ROS production, which suppressed lipogenic transcription factors, C/EBPα and PPARγ. Moreover, the ability of G. cambogia to inhibit ROS production suppressed apoptosis by normalizing the Bcl-2/BAX ratio and PARP cleavage. Lastly, these therapeutic effects of G. cambogia were due to hydroxycitric acid (HCA). These findings provide new insight into the mechanism by which G. cambogia regulates NAFLD progression.

Highlights

Published: 29 July 2021Obesity is a chronic disease resulting from an energy imbalance caused by hypercaloric food intake and insufficient energy expenditure [1] and is strongly associated with type 2 diabetes, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) [2].NAFLD is the most common chronic liver disease in western societies and is well recognized as the hepatic manifestation of metabolic disease [3]
Cambogia inhibited the formation of hepatic lipid droplets and increased liver index, an indicator of NAFLD [46], resulting from High-fat diet (HFD) feeding (Figure 1A)
Since apoptosis is regulated by proapoptotic and antiapoptotic molecules such as Bcl-2 family members related to mitochondrial dysfunction and subsequent caspase-3 activation and cleavage of PARP [51,52,53], we examined the effect of G. cambogia on the alteration of apoptosis-related molecules in free fatty acids (FFAs)-treated HepG2 cells

Summary

Introduction

Obesity is a chronic disease resulting from an energy imbalance caused by hypercaloric food intake and insufficient energy expenditure [1] and is strongly associated with type 2 diabetes, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) [2]. NAFLD is the most common chronic liver disease in western societies and is well recognized as the hepatic manifestation of metabolic disease [3]. NAFLD is characterized by excessive fat accumulation in hepatocytes and is strongly associated with obesity and energy imbalance [4]. If this pathological state is not properly treated, it can progress to non-alcoholic steatohepatitis (NASH) and continue to progress to cirrhosis and to hepatocellular carcinoma [5]. An updated theory is Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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