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

• Published in: Antioxidants Vol. 10; no. 10; p. 1546
• Main Authors: Son, Yiseul, Lee, Heaji, Son, Su-Young, Lee, Choong-Hwan, Kim, Sun-Yeou, Lim, Yunsook
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.09.2021; MDPI
• Subjects: AMPK/Akt-mTOR signaling; Annona muricata; Autophagy; Diabetes; Diabetes mellitus; Diet; Energy metabolism; Experiments; Fatty acids; Glucose; Glucose metabolism; Glucose transporter; hepatic lipid steatosis; High fat diet; Homeostasis; Hyperglycemia; Insulin; Insulin receptor substrate 1; Insulin resistance; Kinases; Lipid metabolism; Lipids; lipophagy; Liver; Metabolism; non-alcoholic fatty liver disease (NAFLD); Oxidation; Oxidative stress; Peroxisome proliferator-activated receptors; Phagocytosis; Streptozocin; TOR protein; type 2 diabetes mellitus (T2DM); United States > US; non-alcoholic fatty liver disease (NAFLD); hepatic lipid steatosis; AMPK/Akt-mTOR signaling; autophagy; lipophagy; Annona muricata; graviola; type 2 diabetes mellitus (T2DM)
• DOI: 10.3390/antiox10101546
• ISSN: 2076-3921

(AM) is evergreen plant of the 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.