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Food Science and Human Wellness 2021, 10(2): 155-162 https://doi.org/10.1016/j.fshw.2021.02.004
Research Article | Open Access | Issue | Published: 22 March 2021

Anti-hyperglycemic effects of dihydromyricetin in streptozotocin-induced diabetic rats

Show Author's Information Maojun Yaoa,c,#,  Hui Tengb,e,#,  Qiyan Lvb,  Huifang Gaob,  Tengming Guob,  Yiwen Linb,  Sihai Gaod( ),  Meihu Mac( ),  Lei Chenb,e( )
College of Chemistry and Chemical Engineering, Jishou University, Jishou, 416000, China
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China
National Research and Development Center for Egg Processing, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070. China
Department of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430070, China
College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524025, China

# Authors contributed equally to this study

Peer review under responsibility of KeAi Communications Co., Ltd

Keywords:
Dihydromyricetin, type 2 diabetes, hypolipidemic, hypoglycemic, AMPK/Akt/GSK-3β signaling pathway
Cite this article:
Yao M, Teng H, Lv Q, et al. Anti-hyperglycemic effects of dihydromyricetin in streptozotocin-induced diabetic rats. Food Science and Human Wellness, 2021, 10(2): 155-162. https://doi.org/10.1016/j.fshw.2021.02.004
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Abstract Full text About this article

Dihydromyricetin (DHM), as a bioactive flavanonol compound, is mainly found in "Tengcha" (Ampelopsis grossedentata) cultivated in south of China. This study aimed to investigate the anti-hyperglycemic and anti-dyslipidemic activities of DHM using type 2 diabetes mellitus (T2D) rats, which was induced by feeding with high fat and fructose diet for 42 days and intraperitoneal administration of streptozocin. Forty-eight freshly-weaned rats were randomly assigned into the negative control (Blank), low dose (100 mg/kg), medium dose (200 mg/kg), high dose (400 mg/kg), and positive (40 mg/kg, met) groups. Fasting blood glucose and body weight were measured at weekly interval. Oral glucose tolerance tests were performed on days 42. The results revealed that DHM possessed significant antihyperglycaemic and antihyperinsulinemic effects. Moreover, after the DHM treatment, p-Akt and p-AMPK expression was upregulated, and glycogen synthase kinase-3β (GSK-3β) expression was downregulated, indicating that the potential anti-diabetic mechanism of DHM might be due to the regulation of the AMPK/Akt/GSK-3β signaling pathway.


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About this article

Anti-hyperglycemic effects of dihydromyricetin in streptozotocin-induced diabetic rats

Show Author's information Maojun Yaoa,c,#, Hui Tengb,e,#, Qiyan Lvb, Huifang Gaob, Tengming Guob, Yiwen Linb, Sihai Gaod( ), Meihu Mac( ), Lei Chenb,e( )
College of Chemistry and Chemical Engineering, Jishou University, Jishou, 416000, China
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China
National Research and Development Center for Egg Processing, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070. China
Department of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430070, China
College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524025, China

# Authors contributed equally to this study

Peer review under responsibility of KeAi Communications Co., Ltd

Abstract

Dihydromyricetin (DHM), as a bioactive flavanonol compound, is mainly found in "Tengcha" (Ampelopsis grossedentata) cultivated in south of China. This study aimed to investigate the anti-hyperglycemic and anti-dyslipidemic activities of DHM using type 2 diabetes mellitus (T2D) rats, which was induced by feeding with high fat and fructose diet for 42 days and intraperitoneal administration of streptozocin. Forty-eight freshly-weaned rats were randomly assigned into the negative control (Blank), low dose (100 mg/kg), medium dose (200 mg/kg), high dose (400 mg/kg), and positive (40 mg/kg, met) groups. Fasting blood glucose and body weight were measured at weekly interval. Oral glucose tolerance tests were performed on days 42. The results revealed that DHM possessed significant antihyperglycaemic and antihyperinsulinemic effects. Moreover, after the DHM treatment, p-Akt and p-AMPK expression was upregulated, and glycogen synthase kinase-3β (GSK-3β) expression was downregulated, indicating that the potential anti-diabetic mechanism of DHM might be due to the regulation of the AMPK/Akt/GSK-3β signaling pathway.

Keywords: Dihydromyricetin, type 2 diabetes, hypolipidemic, hypoglycemic, AMPK/Akt/GSK-3β signaling pathway

References(41)

[1]

L. Chen, X. Lin, X. Fan, et al., A self-emulsifying formulation of Sonchus oleraceus Linn for an improved anti-diabetic effect in vivo, Food Funct. 11 (1) (2020) 1225-1229. https://doi.org/10.1039/c9fo00772e.
DOI Google Scholar
[2]

C. Francesca, B. Ryotaro, K.M.J. Young, et al., Evidence of β-cell dedifferentiation in human type 2 diabetes, J. Clin. Endocrinol. Metab. 101 (3) (2016) 1044-1054. https://doi.org/10.1210/jc.2015-2860.
DOI Google Scholar
[3]

S. Gao, Q. Guo, C. Qin, et al., Sea buckthorn fruit oil extract alleviates insulin resistance through the PI3K/Akt signaling pathway in type 2 diabetes mellitus cells and rats, J. Agric. Food Chem. 65 (7) (2017) 1328-1336. https://doi.org/10.1021/acs.jafc.6b04682.
DOI Google Scholar
[4]

K. Martinez, S. Lockhart, M. Davies, et al., Diabetes distress, illness perceptions and glycaemic control in adults with type 2 diabetes, Psychol. Health Med. 23 (2) (2018) 171-177. https://doi.org/10.1080/13548506.2017.1339892.
DOI Google Scholar
[5]

R.A. Harrigan, M.S. Nathan, P. Beattie, Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment, Ann. Emerg. Med. 38 (1) (2001) 68-78. https://doi.org/10.1067/mem.2001.114314.
DOI Google Scholar
[6]
J. Zhou, G. Xie, X. Yan, et al., Traditional Chinese medicines: molecular structures, natural sources, and applications, Ashgate (2003) 1st Edition. https://doi.org/10.1038/srep36184.
[7]

L. Le, B. Jiang, W. Wan, et al., Metabolomics reveals the protective of dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity, Sci. Rep. 6 (2016) 36184. https://doi.org/10.1038/srep36184.
DOI Google Scholar
[8]

Z. Zhang, X. Wang, M. Zhao, et al., Optimization of polysaccharides extraction from Clematis huchouensis Tamura and its antioxidant activity, Carbohydr. Polym. 111 (20) (2014) 762-767. https://doi.org/10.1016/j.carbpol.2014.04.103.
DOI Google Scholar
[9]

D. Wu, S. Mei, R. Duan, et al., How black tea pigment theaflavin dyes chicken eggs: binding affinity study of theaflavin with ovalbumin, Food Chem. 303 (15) (2020) 1-8. https://doi.org/10.1016/j.foodchem.2019.125407.
DOI Google Scholar
[10]

L. Shi, T. Zhang, X. Liang, et al., Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway, Mol. Cell. Endocrinol. 409(92-102) (2015). https://doi.org/10.1016/j.mce.2015.03.009.
DOI Google Scholar
[11]

L. Chen, H. Teng, H. Cao, Chlorogenic acid and caffeic acid from Sonchus oleraceus Linn synergistically attenuate insulin resistance and modulate glucose uptake in HepG2 cells, Food Chem. Toxicol. 127 (2019) 182-187. https://doi.org/10.1016/j.fct.2019.03.038.
DOI Google Scholar
[12]

I.M. Libman, E. Barinas-Mitchell, A. Bartucci, et al., Reproducibility of the oral glucose tolerance test in overweight children, J. Clin. Endocrinol. Metab. 93 (11) (2008) 4231-4237. https://doi.org/10.1210/jc.2008-0801.
DOI Google Scholar
[13]

F. Geng, Y.X. Xie, J.Q. Wang, et al., N-glycoproteomic analysis of chicken egg yolk, J. Agric. Food Chem. 66 (43) (2018) 11510-11516. https://doi.org/10.1021/acs.jafc.8b04492.
DOI Google Scholar
[14]

X. Liu, J. Wang, Q. Huang, et al., Underlying mechanism for the differences in heat-induced gel properties between thick egg whites and thin egg whites: gel properties, structure and quantitative proteome analysis, Food Hydrocoll. 106 (2020) 105873. https://doi.org/10.1016/j.foodhyd.2020.105873.
DOI Google Scholar
[15]

J. Revathy, S. Srinivasan, S.H.S. Abdullah, et al., Antihyperglycemic effect of hesperetin, a citrus flavonoid, extenuates hyperglycemia and exploring the potential role in antioxidant and antihyperlipidemic in streptozotocin-induced diabetic rats, Biomed. Pharmacother. 97 (2018) 98-106. https://doi.org/10.1016/j.biopha.2017.10.102.
DOI Google Scholar
[16]

A. Ben Hsouna, S. Mongi, G. Culioli, et al., Protective effects of ethyl acetate fraction of Lawsonia inermis fruits extract against carbon tetrachloride-induced oxidative damage in rat liver, Toxicol. Ind. Health 32 (4) (2016) 694-706. https://doi.org/10.1177/0748233713502839.
DOI Google Scholar
[17]

L.A. BenSaad, K.H. Kim, C.C. Quah, et al., Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A & B isolated from Punica granatum, BMC Complement Altern. Med. 17 (1) (2017) 47. https://doi.org/10.1186/s12906-017-1555-0.
DOI Google Scholar
[18]

C.R.L. Cardoso, J.V. Melo, G.C. Salles, et al., Prognostic impact of the ankle-brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the rio de janeiro type 2 diabetes cohort study, Diabetologia 61 (11) (2018) 2266-2276. https://doi.org/10.1007/s00125-018-4709-9.
DOI Google Scholar
[19]

A.D. Association, 4. Lifestyle Management: <em>Standards of Medical Care in Diabetes—2018, Diabetes Care 41 (Supplement 1) (2018) S38-S50. https://doi.org/10.2337/dc18-S004.
DOI Google Scholar
[20]

L. Chen, X. Fan, X. Lin, et al., Phenolic extract from Sonchus oleraceus L. protects diabetes-related liver injury in rats through TLR4/NF-κB signaling pathway, eFood 1 (1) (2019) 77-84. https://doi.org/10.2991/efood.k.191018.002.
DOI Google Scholar
[21]

L. Chen, X. Lin, X. Fan, et al., Sonchus oleraceus Linn extract enhanced glucose homeostasis through the AMPK/Akt/GSK-3β signaling pathway in diabetic liver and HepG2 cell culture, Food Chem. Toxicol. 136 (2020) 111072. https://doi.org/10.1016/j.fct.2019.111072.
DOI Google Scholar
[22]

S.M. Jang, S.T. Yee, J. Choi, et al., Ursolic acid enhances the cellular immune system and pancreatic β-cell function in streptozotocin-induced diabetic mice fed a high-fat diet, Int. Immunopharmacol. 9 (1) (2009) 113-119. https://doi.org/10.1016/j.intimp.2008.10.013.
DOI Google Scholar
[23]

P. Jian Gang, L. Mo, Y. Lu, et al., Diabetes mellitus and the risk of prostate cancer: an update and cumulative meta-analysis, Endocr. J. 40 (1) (2015) 54-61. https://doi.org/10.3109/07435800.2014.934961.
DOI Google Scholar
[24]

L.H. Storlien, A.B. Jenkins, D.J. Chisholm, et al., Influence of dietary fat composition on development of insulin resistance in rats: relationship to muscle triglyceride and ω-3 fatty acids in muscle phospholipid, Diabetes 40 (2) (1991) 280-289. https://doi.org/10.2337/diab.40.2.280.
DOI Google Scholar
[25]

T.Y. Reuter, Diet-induced models for obesity and type 2 diabetes, Dis. Model Mech. 4 (1) (2008) 3-8. https://doi.org/10.1016/j.ddmod.2007.09.004.
DOI Google Scholar
[26]

R.D. Wilson, M.S. Islam, Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes, Pharmacol. Rep. 64 (1) (2012) 129-139. https://doi.org/10.1016/s1734-1140(12)70739-9.
DOI Google Scholar
[27]

Y.Q. Song, J.E. Manson, L. Tinker, et al., Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women - The Women's Health Initiative Observational Study, Diabetes Care 30 (7) (2007) 1747-1752. https://doi.org/10.2337/dc07-0358.
DOI Google Scholar
[28]

N.N. Than, P.N. Newsome, A concise review of non-alcoholic fatty liver disease, Atherosclerosis 239 (1) (2015) 192-202. https://doi.org/10.1016/j.atherosclerosis.2015.01.001.
DOI Google Scholar
[29]

L. Liu, J. Wan, H. Lang, et al., Dihydromyricetin delays the onset of hyperglycemia and ameliorates insulin resistance without excessive weight gain in Zucker diabetic fatty rats, Mol. Cell. Endocrinol. 439 (2017) 105-115. https://doi.org/10.1016/j.mce.2016.10.028.
DOI Google Scholar
[30]

G. Marchesini, M. Brizi, G. Bianchi, Nonalcoholic fatty liver disease: a feature of the metabolic syndrome, Diabetes 50 (8) (2001) 1844-1850. https://doi.org/10.2337/diabetes.50.8.1844.
DOI Google Scholar
[31]

E. Bugianesi, A.J. Mccullough, G. Marchesini, Insulin resistance: a metabolic pathway to chronic liver disease, Hepatology 42 (5) (2010) 987-1000. https://doi.org/10.1002/hep.20920.
DOI Google Scholar
[32]

R.J. Perry, V.T. Samuel, K.F. Petersen, et al., The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes, Nature 510 (7503) (2014) 84-91. https://doi.org/10.1038/nature13478.
DOI Google Scholar
[33]

A.K. Chaudhary, S. Ahmad, A. Mazumder, Cognitive enhancement in aged mice after chronic administration of Cedrus deodara Loud. and Pinus roxburghii Sarg. with demonstrated antioxidant properties, J. Nat. Med. 68 (2) (2014) 274-283. https://doi.org/10.1007/s11418-013-0775-y.
DOI Google Scholar
[34]

E. Ikonen, Mechanisms for cellular cholesterol transport: defects and human disease, Physiol. Rev. 86 (4) (2006) 1237-1261. https://doi.org/10.1152/physrev.00022.2005.
DOI Google Scholar
[35]

H.M. O'Neill, S.J. Maarbjerg, J.D. Crane, et al., AMP-activated protein kinase (AMPK) β1β2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise, Proc. Natl. Acad. Sci. U. S. A. 108 (38) (2011) 16092-16097. https://doi.org/10.1073/pnas.1105062108.
DOI Google Scholar
[36]

I. Sahra, K. Laurent, A. Loubat, et al., The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level, Oncogene 27 (25) (2008) 3576-3586. https://doi.org/10.1038/sj.onc.1211024.
DOI Google Scholar
[37]

T. Kim, J. Davis, A.J. Zhang, et al., Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells, Biochem. Biophys. Res. Commun. 388 (2) (2009) 377-382. https://doi.org/10.1016/j.bbrc.2009.08.018.
DOI Google Scholar
[38]

R. Varshney, S. Gupta, P. Roy, Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway, Mol. Cell. Endocrinol. 448 (2017) 1-20. https://doi.org/10.1016/j.mce.2017.02.033.
DOI Google Scholar
[39]

D.W. Huang, W.C. Chang, S.B. Wu, et al., Vescalagin from pink wax apple [Syzygium samarangense (blume) merrill and perry] alleviates hepatic insulin resistance and ameliorates glycemic metabolism abnormality in rats fed a high-fructose diet, J. Agric. Food Chem. 64 (5) (2016) 1122-1129. https://doi.org/10.1021/acs.jafc.5b05558.
DOI Google Scholar
[40]

L. Goedeke, R.J. Perry, G.I. Shulman, Emerging pharmacological targets for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes, Annu. Rev. Pharmacol. Toxicol. 59 (1) (2019) 65-87. https://doi.org/10.1146/annurev-pharmtox-010716-104727.
DOI Google Scholar
[41]

I. Cordero-Herrera, M.Á. Martín, L. Goya, et al., Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells, Food Chem. Toxicol. 64 (2) (2014) 10-19. https://doi.org/10.1016/j.fct.2013.11.014.
DOI Google Scholar
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Publication history

Received: 20 March 2020
Revised: 07 July 2020
Accepted: 07 July 2020
Published: 22 March 2021
Issue date: March 2021

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© 2021 Beijing Academy of Food Sciences.

Acknowledgements

This work is supported by the National Natural Science Foundation of China (NSFC, Grant No. 31801459; 31701520), Science and Technology General Projects of Fujian Province (2019J01393), Educational research project for young and middle-aged teachers in Fujian Province (JT180116).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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