Ameliorative Effect of Annona muricata (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice.

Yiseul Son,Choong-Hwan Lee,Su-Young Son,Sun-Yeou Kim,Heaji Lee,Yunsook Lim

doi:10.3390/antiox10101546

Yiseul Son, Choong-Hwan Lee + Show 4 more

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https://doi.org/10.3390/antiox10101546

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Abstract

Annona muricata (AM) is evergreen plant of the Annonaceae family and known to have anticancer and antidiabetic effects. However, anti-diabetic mechanisms of AM extracts (AME) associated with hepatic glucose regulation and lipid metabolism remain unclear. In this study, we investigated the protective effect of AME extracted on hepatic damage in diabetic mice. Diabetes was induced by a high-fat diet with two-times streptozotocin (STZ) injection (60 mg/kg BW) in C57BL/6 male mice. The diabetic mice were daily administered with AME (50 or 100 mg/kg BW) by gavage for 9 weeks. Biomarkers related to energy metabolism and insulin signaling were examined to identify the effect of AME on hyperglycemia induced hepatic damage. AME supplementation reduced levels of FBG, HbA1c, HOMA-IR and hepatic lipid profiles as well as enhanced insulin signaling by increased the protein levels of IRS-1 accompanied GLUT2 in diabetic mice. Especially low dose of AME showed the beneficial effect of reducing oxidative stress (4-HNE, protein carbonyls, Nrf2, NQO1) and improved hepatic morphology demonstrated by lipid droplets along with upregulation of lipophagy (pAMPK, p-mTOR/mTOR, LC3-2/LC3-1) in diabetic mice. Moreover, AME supplementation ameliorated hepatic lipid metabolism (FAS, SREBP1c, C/EBPα, PPARγ, CPT1A, PPARα) and energy metabolism (pAMPK, PGC1α) in diabetic mice. Taken together, this study suggested that AME could be helpful to prevent hepatic abnormality by regulation of insulin signaling associated with energy metabolism and autophagy in diabetes.

Highlights

Type 2 diabetes mellitus (T2DM), called non-insulin dependent diabetes, is a chronic disease that occurs when the body cannot effectively use the insulin it produces [1]
The present study indicated that AM extracts (AME) exhibits antioxidants and hypoglycemic properties
The results suggest that AME supplementation could control hepatic lipid homeostasis along with lipophagy activation and AMPK-mTOR pathway in diabetic condition

Summary

Introduction

Type 2 diabetes mellitus (T2DM), called non-insulin dependent diabetes, is a chronic disease that occurs when the body cannot effectively use the insulin it produces [1]. Common symptoms of T2DM are hyperglycemia and dyslipidemia, which cause multi-organ damage in the body [3]. The liver is an insulin-sensitive tissue and is highly susceptible to hyperglycemic-induced oxidative stress that can cause tissue damage [4]. T2DM was known as a risk factor for several liver diseases such as non-alcoholic fatty liver disease (NAFLD), hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [5,6,7,8]. Insulin resistance in T2DM patients leads to an imbalance in hepatic lipid metabolism

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