Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice
<i>Annona muricata</i> (AM) is evergreen plant of the <i>Annonaceae</i> 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...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/10/1546 |
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| author | Yiseul Son Heaji Lee Su-Young Son Choong-Hwan Lee Sun-Yeou Kim Yunsook Lim |
| author_facet | Yiseul Son Heaji Lee Su-Young Son Choong-Hwan Lee Sun-Yeou Kim Yunsook Lim |
| author_sort | Yiseul Son |
| collection | DOAJ |
| description | <i>Annona muricata</i> (AM) is evergreen plant of the <i>Annonaceae</i> 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. |
| first_indexed | 2024-03-10T06:46:03Z |
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| id | doaj.art-34770f0929254be1aa81ed2f7c133960 |
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| language | English |
| last_indexed | 2024-03-10T06:46:03Z |
| publishDate | 2021-09-01 |
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| series | Antioxidants |
| spelling | doaj.art-34770f0929254be1aa81ed2f7c1339602023-11-22T17:15:38ZengMDPI AGAntioxidants2076-39212021-09-011010154610.3390/antiox10101546Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic MiceYiseul Son0Heaji Lee1Su-Young Son2Choong-Hwan Lee3Sun-Yeou Kim4Yunsook Lim5Department of Food and Nutrition, Kyung Hee University, 26 Kyung Hee-Daero, Seoul 02447, KoreaDepartment of Food and Nutrition, Kyung Hee University, 26 Kyung Hee-Daero, Seoul 02447, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaGachon Institute of Pharmaceutical Science, Gachon University, #191, Hambakmoero, Incheon 21936, KoreaDepartment of Food and Nutrition, Kyung Hee University, 26 Kyung Hee-Daero, Seoul 02447, Korea<i>Annona muricata</i> (AM) is evergreen plant of the <i>Annonaceae</i> 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.https://www.mdpi.com/2076-3921/10/10/1546type 2 diabetes mellitus (T2DM)hepatic lipid steatosisnon-alcoholic fatty liver disease (NAFLD)lipophagyautophagyAMPK/Akt-mTOR signaling |
| spellingShingle | Yiseul Son Heaji Lee Su-Young Son Choong-Hwan Lee Sun-Yeou Kim Yunsook Lim Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice Antioxidants type 2 diabetes mellitus (T2DM) hepatic lipid steatosis non-alcoholic fatty liver disease (NAFLD) lipophagy autophagy AMPK/Akt-mTOR signaling |
| title | Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice |
| title_full | Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice |
| title_fullStr | Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice |
| title_full_unstemmed | Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice |
| title_short | Ameliorative Effect of <i>Annona muricata</i> (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice |
| title_sort | ameliorative effect of i annona muricata i graviola extract on hyperglycemia induced hepatic damage in type 2 diabetic mice |
| topic | type 2 diabetes mellitus (T2DM) hepatic lipid steatosis non-alcoholic fatty liver disease (NAFLD) lipophagy autophagy AMPK/Akt-mTOR signaling |
| url | https://www.mdpi.com/2076-3921/10/10/1546 |
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