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http://dx.doi.org/10.4162/nrp.2018.12.1.20

Anti-hyperglycemic effects and signaling mechanism of Perilla frutescens sprout extract  

Kim, Da-Hye (Jeonju AgroBio-Materials Institute)
Kim, Sang Jun (Jeonju AgroBio-Materials Institute)
Yu, Kang-Yeol (Jeonju AgroBio-Materials Institute)
Jeong, Seung-Il (Jeonju AgroBio-Materials Institute)
Kim, Seon-Young (Jeonju AgroBio-Materials Institute)
Publication Information
Nutrition Research and Practice / v.12, no.1, 2018 , pp. 20-28 More about this Journal
Abstract
BACKGROUND/OBJECTIVES: Perilla frutescens (L.) Britton var. (PF) sprout is a plant of the labiate family. We have previously reported the protective effects of PF sprout extract on cytokine-induced ${\beta}-cell$ damage. However, the mechanism of action of the PF sprout extract in type 2 diabetes (T2DM) has not been investigated. The present study was designed to study the effects of PF sprout extract and signaling mechanisms in the T2DM mice model using C57BL/KsJ-db/db (db/db) mice. MATERIALS/METHODS: Male db/db mice were orally administered PF sprout extract (100, 300, and 1,000 mg/kg of body weight) or rosiglitazone (RGZ, positive drug, 1 mg/kg of body weight) for 4 weeks. Signaling mechanisms were analyzed using liver tissues and HepG2 cells. RESULTS: The PF sprout extract (300 and 1,000 mg/kg) significantly reduced the fasting blood glucose, serum insulin, triglyceride and total cholesterol levels in db/db mice. PF sprout extract also significantly improved glucose intolerance and insulin sensitivity, decreased hepatic gluconeogenic protein expression, and ameliorated histological alterations of the pancreas and liver. Levels of phosphorylated AMP-activated protein kinase (AMPK) protein expression also increased in the liver after treatment with the extract. In addition, an increase in the phosphorylation of AMPK and decrease in the phosphoenolpyruvate carboxykinase and glucose 6-phosphatase proteins in HepG2 cells were also observed. CONCLUSIONS: Our results sugges that PF sprout displays beneficial effects in the prevention and treatment of type 2 diabetes via modulation of the AMPK pathway and inhibition of gluconeogenesis in the liver.
Keywords
Perilla frutescens; diabetes mellitus; gluconeogenesis;
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1 Kurita N, Koike S. Synergistic antimicrobial effect of acetic acid, sodium chloride and essential oil components. Agric Biol Chem 1982;46:1655-60.
2 Ueda H, Yamazaki C, Yamazaki M. Inhibitory effect of Perilla leaf extract and luteolin on mouse skin tumor promotion. Biol Pharm Bull 2003;26:560-3.   DOI
3 Makino T, Furuta Y, Wakushima H, Fujii H, Saito K, Kano Y. Anti-allergic effect of Perilla frutescens and its active constituents. Phytother Res 2003;17:240-3.   DOI
4 Banno N, Akihisa T, Tokuda H, Yasukawa K, Higashihara H, Ukiya M, Watanabe K, Kimura Y, Hasegawa J, Nishino H. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem 2004;68:85-90.   DOI
5 Pasko P, Sajewicz M, Gorinstein S, Zachwieja Z. Analysis of selected phenolic acids and flavonoids in Amaranthus cruentus and Chenopodium quinoa seeds and sprouts by HPLC. Acta Chromatogr 2008;20:661-72.   DOI
6 Lucarini R, Bernardes WA, Ferreira DS, Tozatti MG, Furtado R, Bastos JK, Pauletti PM, Januario AH, Silva ML, Cunha WR. In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts, rosmarinic acid and its acetyl ester derivative. Pharm Biol 2013;51:1087-90.   DOI
7 Karthikkumar V, Sivagami G, Vinothkumar R, Rajkumar D, Nalini N. Modulatory efficacy of rosmarinic acid on premalignant lesions and antioxidant status in 1,2-dimethylhydrazine induced rat colon carcinogenesis. Environ Toxicol Pharmacol 2012;34:949-58.   DOI
8 Pereira P, Tysca D, Oliveira P, da Silva Brum LF, Picada JN, Ardenghi P. Neurobehavioral and genotoxic aspects of rosmarinic acid Pharmacol Res 2005;52:199-203.   DOI
9 Runtuwene J, Cheng KC, Asakawa A, Amitani H, Amitani M, Morinaga A, Takimoto Y, Kairupan BH, Inui A. Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4. Drug Des Devel Ther 2016;10:2193-202.   DOI
10 Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 2008;10 Suppl 4:32-42.   DOI
11 Valenti L, Bugianesi E, Pajvani U, Targher G. Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes? Liver Int 2016; 36:1563-79.   DOI
12 Collins QF, Liu HY, Pi J, Liu Z, Quon MJ, Cao W. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5'-AMP-activated protein kinase. J Biol Chem 2007;282:30143-9.   DOI
13 Govindaraj J, Sorimuthu Pillai S. Rosmarinic acid modulates the antioxidant status and protects pancreatic tissues from glucolipotoxicity mediated oxidative stress in high-fat diet: streptozotocininduced diabetic rats. Mol Cell Biochem 2015;404:143-59.   DOI
14 Kwon YI, Vattem DA, Shetty K. Evaluation of clonal herbs of Lamiaceae species for management of diabetes and hypertension. Asia Pac J Clin Nutr 2006;15:107-18.
15 Giandalia A, Romeo EL, Ruffo MC, Muscianisi M, Giorgianni L, Forte F, Cucinotta D, Russo GT. Clinical correlates of persistently elevated liver enzymes in type 2 diabetic outpatients. Prim Care Diabetes 2017;11:226-32.   DOI
16 Huang M, Zhao P, Xiong M, Zhou Q, Zheng S, Ma X, Xu C, Yang J, Yang X, Zhang TC. Antidiabetic activity of perylenequinonoid-rich extract from Shiraia bambusicola in KK-Ay mice with spontaneous type 2 diabetes mellitus. J Ethnopharmacol 2016;191:71-81.   DOI
17 Sanaei M, Ebrahimi M, Banazadeh Z, Shafiee G, Khatami F, Ahadi Z, Heshmat R. Consequences of AphanizomenonFlos-aquae(AFA) extract (Stemtech (TM) ) on metabolic profile of patients with type 2 diabetes. J Diabetes Metab Disord 2015;14:50.   DOI
18 Sen S, Querques MA, Chakrabarti S. North American Ginseng (Panax quinquefolius) prevents hyperglycemia and associated pancreatic abnormalities in diabetes. J Med Food 2013;16:587-92.   DOI
19 Yki Jarvinen H. Glucose toxicity. Endocr Rev 1992;13:415-31.
20 Bae UJ, Park SH, Jung SY, Park BH, Chae SW. Hypoglycemic effects of aqueous persimmon leaf extract in a murine model of diabetes. Mol Med Rep 2015;12:2547-54.   DOI
21 Hsu YJ, Lee TH, Chang CL, Huang YT, Yang WC. Anti-hyperglycemic effects and mechanism of Bidens pilosa water extract. J Ethnopharmacol 2009;122:379-83.   DOI
22 Nyarko AK, Asare-Anane H, Ofosuhene M, Addy ME. Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated pancreatic beta-islet cells. Phytomedicine 2002;9:346-51.   DOI
23 Zheng J, Woo SL, Hu X, Botchlett R, Chen L, Huo Y, Wu C. Metformin and metabolic diseases: a focus on hepatic aspects. Front Med 2015;9:173-86.   DOI
24 Derosa G, Maffioli P. ${\alpha}$-Glucosidase inhibitors and their use in clinical practice. Arch Med Sci 2012;8:899-906.
25 Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 2011;13:1016-23.   DOI
26 Molavi B, Rassouli N, Bagwe S, Rasouli N. A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications. Vasc Health Risk Manag 2007;3:967-73.
27 Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287:360-72.   DOI
28 Vidal-Puig A, O'Rahilly S. Metabolism. Controlling the glucose factory. Nature 2001;413:125-6.   DOI
29 Koo, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S, Hedrick S, Xu W, Boussouar F, Brindle P, Takemori H, Montminy M. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005;437:1109-11.   DOI
30 Lochhead PA, Salt IP, Walker KS, Hardie DG, Sutherland C. 5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes 2000;49:896-903.   DOI