Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats

Sarikaphuti,Ariya; Nararatwanchai,Thamthiwat; Hashiguchi,Teruto; Ito,Takashi; Thaworanunta,Sita; Kikuchi,Kiyoshi; Oyama,Yoko; Maruyama,Ikuro; Tancharoen,Salunya

doi:10.3892/etm.2013.1203

Preventive effects of Morus alba L. anthocyanins on diabetes in Zucker diabetic fatty rats

Authors:
- Ariya Sarikaphuti
- Thamthiwat Nararatwanchai
- Teruto Hashiguchi
- Takashi Ito
- Sita Thaworanunta
- Kiyoshi Kikuchi
- Yoko Oyama
- Ikuro Maruyama
- Salunya Tancharoen
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Affiliations: School of Anti‑Aging and Regenerative Medicine, Mae Fah Luang University, Bangkok 10110, Thailand, Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Prosthodontics, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand, Departments of Physiology and Neurosurgery, Kurume University School of Medicine, Fukuoka 830‑0011, Japan, Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand
Published online on: July 4, 2013 https://doi.org/10.3892/etm.2013.1203
Pages: 689-695

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Abstract

The mulberry plant (Morus alba L.) contains abundant anthocyanins (ANCs), which are natural antioxidants. The aim of this study was to determine the ANC composition of Thai Morus alba L. fruits and to assess the effect of an ANC extract on blood glucose and insulin levels in male leptin receptor‑deficient Zucker diabetic fatty (ZDF) rats. The major components of the ANC extract were identified by high‑performance liquid chromatography‑electrospray ionization‑mass spectrometry. ZDF and lean rats were treated with 125 or 250 mg ANCs/kg body weight, or 1% carboxymethylcellulose (CMC) twice daily for 5 weeks. Neither ANC dose had an effect on body weight. Following 5 weeks of treatment, glucose levels were observed to increase from 105.5±8.7 to 396.25±21 mg/dl (P<0.0001) in the CMC‑treated ZDF rats; however, the glucose levels were significantly lower in the rats treated with 125 or 250 mg/kg ANCs (228.25±45 and 131.75±10 mg/dl, respectively; P<0.001 versus CMC). The administration of 250 mg/kg ANCs normalized glucose levels in the ZDF rats towards those of the lean littermates. Insulin levels were decreased significantly in the ZDF rats treated with CMC or 125 mg/kg ANCs (P<0.0001), but not in the rats treated with 250 mg/kg ANCs. Histologically, 250 mg/kg ANCs was observed to prevent islet degeneration compared with the islets in CMC‑treated rats. This study, demonstrated that ANCs extracted from Morus alba L. were well tolerated and exhibited effective anti‑diabetic properties in ZDF rats. ANCs represent a promising class of therapeutic compounds that may be useful in the prevention of type 2 diabetes.

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1	Jun H, Bae HY, Lee BR, et al: Pathogenesis of non-insulin-dependent (type II) diabetes mellitus (NIDDM) - genetic predisposition and metabolic abnormalities. Adv Drug Deliv Rev. 35:157–177. 1999. View Article : Google Scholar : PubMed/NCBI
2	Rosak C: The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents. J Diabetes Complications. 16:123–132. 2002. View Article : Google Scholar : PubMed/NCBI
3	Jennings AM, Wilson RM and Ward JD: Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents. Diabetes Care. 12:203–208. 1989. View Article : Google Scholar : PubMed/NCBI
4	Xia X, Ling W, Ma J, et al: An anthocyanin-rich extract from black rice enhances atherosclerotic plaque stabilization in apolipoprotein E-deficient mice. J Nutr. 136:2220–2225. 2006.PubMed/NCBI
5	Wallace TC: Anthocyanins in cardiovascular disease. Adv Nutr. 2:1–7. 2011. View Article : Google Scholar
6	Wang LS and Stoner GD: Anthocyanins and their role in cancer prevention. Cancer Lett. 269:281–290. 2008. View Article : Google Scholar : PubMed/NCBI
7	Grace MH, Ribnicky DM, Kuhn P, et al: Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, Vaccinium angustifolium Aiton. Phytomedicine. 16:406–415. 2009. View Article : Google Scholar : PubMed/NCBI
8	Jayaprakasam B, Vareed SK, Olson LK and Nair MG: Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. J Agric Food Chem. 53:28–31. 2005. View Article : Google Scholar : PubMed/NCBI
9	Duthie G and Crozier A: Plant-derived phenolic antioxidants. Curr Opin Clin Nutr Metab Care. 3:447–451. 2000. View Article : Google Scholar
10	Kaewkaen P, Tong-Un T, Wattanathorn J, et al: Mulberry fruit extract protects against memory impairment and hippocampal damage in animal model of vascular dementia. Evid Based Complement Alternat Med. 2012:2635202012. View Article : Google Scholar : PubMed/NCBI
11	Andallu B, Kumar AV and Varadacharyulu NC: Oxidative stress in streptozocin-diabetic rats: Amelioration by mulberry (Morus Indica L.) leaves. Chin J Integr Med. Dec 22–2012.(Epub ahead of print).
12	Musabayane CT, Bwititi PT and Ojewole JA: Effects of oral administration of some herbal extracts on food consumption and blood glucose levels in normal and streptozotocin-treated diabetic rats. Methods Find Exp Clin Pharmacol. 28:223–228. 2006. View Article : Google Scholar : PubMed/NCBI
13	Du Q, Zheng J and Xu Y: Composition of anthocyanins in mulberry and their antioxidant activity. J Food Compost Anal. 21:390–395. 2008. View Article : Google Scholar
14	Peng CH, Liu LK, Chuang CM, Chyau CC, Huang CN and Wang CJ: Mulberry water extracts possess an anti-obesity effect and ability to inhibit hepatic lipogenesis and promote lipolysis. J Agric Food Chem. 59:2663–2671. 2011. View Article : Google Scholar : PubMed/NCBI
15	Chen PN, Chu SC, Chiou HL, Kuo WH, Chiang CL and Hsieh YS: Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett. 235:248–259. 2006. View Article : Google Scholar : PubMed/NCBI
16	Ha US, Bae WJ, Kim SJ, et al: Protective effect of cyanidin-3-O-β-D-glucopyranoside fraction from mulberry fruit pigment against oxidative damage in streptozotocin-induced diabetic rat bladder. Neurourol Urodyn. Nov 25–2012.(Epub ahead of print).
17	Clark JB, Palmer CJ and Shaw WN: The diabetic Zucker fatty rat. Proc Soc Exp Biol Med. 173:68–75. 1983. View Article : Google Scholar
18	Mega C, de Lemos ET, Vala H, et al: Diabetic nephropathy amelioration by a low-dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat). Exp Diabetes Res. 2011:1620922011. View Article : Google Scholar : PubMed/NCBI
19	Yu X, Zhao M, Hu J, Zeng S and Bai X: Correspondence analysis of antioxidant activity and UV-Vis absorbance of Maillard reaction products as related to reactants. LWT - Food Science and Technology. 46:1–9. 2012. View Article : Google Scholar
20	Zhang M, Chen H, Li J, Pei Y and Liang Y: Antioxidant properties of tartary buckwheat extracts as affected by different thermal processing methods. LWT - Food Science and Technology. 43:181–185. 2010. View Article : Google Scholar
21	Sutharut J and Sudarat J: Total anthocyanin content and antioxidant activity of germinated colored rice. International Food Research Journal. 19:215–221. 2012.
22	Nizamutdinova IT, Jin YC, Chung JI, et al: The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis. Mol Nutr Food Res. 53:1419–1429. 2009. View Article : Google Scholar : PubMed/NCBI
23	Qin C, Li Y, Niu W, Ding Y, Zhang R and Shang X: Analysis and characterisation of anthocyanins in mulberry fruit. Czech J Food Sci. 28:117–126. 2010.
24	Jones HB, Nugent D and Jenkins R: Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains. Int J Exp Pathol. 91:288–301. 2010. View Article : Google Scholar : PubMed/NCBI
25	Pick A, Clark J, Kubstrup C, Levisetti M, Pugh W, Bonner-Weir S and Polonsky KS: Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat. Diabetes. 47:358–364. 1998. View Article : Google Scholar : PubMed/NCBI
26	Wei X, Wang D, Yang Y, et al: Cyanidin-3-O-β-glucoside improves obesity and triglyceride metabolism in KK-Ay mice by regulating lipoprotein lipase activity. J Sci Food Agric. 91:1006–1013. 2011.
27	Inaguma T, Han J and Isoda H: Improvement of insulin resistance by Cyanidin 3-glucoside, anthocyanin from black beans through the up-regulation of GLUT4 gene expression. BMC Proc. 5(Suppl 8): P212011. View Article : Google Scholar
28	Nizamutdinova IT, Jin YC, Chung JI, Shin SC, Lee SJ, Seo HG, Lee JH, Chang KC and Kim HJ: The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis. Mol Nutr Food Res. 53:1419–1429. 2009. View Article : Google Scholar : PubMed/NCBI
29	Janssen SW, Hermus AR, Lange WP, et al: Progressive histopathological changes in pancreatic islets of Zucker Diabetic Fatty rats. Exp Clin Endocrinol Diabetes. 109:273–282. 2001. View Article : Google Scholar : PubMed/NCBI