Antidiabetic and Antihyperlipidemic Activity of β-carotene on Streptozotocin-induced Diabetic Rats

Khadiza Khanam

Department of Pharmacy, Faculty of Science and Engineering, Varendra University, Rajshahi, Bangladesh.

A. H. M. Mostofa Kamal

Rajshashi Medical College Hospital, Rajshahi, Bangladesh.

Mim Yeasmin

Department of Pharmacy, Faculty of Science and Engineering, Varendra University, Rajshahi, Bangladesh.

Sultana Rajia *

Center for Interdisciplinary Research (CIR), Varendra University, Rajshahi, Bangladesh.

*Author to whom correspondence should be addressed.


Abstract

Objective: A vital anti-oxidant, β-carotene has the capacity to reduce reactive oxidative stress, metabolic syndrome such as Type 2 (T2) Diabetes Mellitus (DM) and prevent inflammation, obesity, alzheimer and cardiovascular diseases in human. In this study, we evaluated the efficacy of β-carotene on streptozotocin (STZ)- induced T2DM rats.

Methods: Diabetes was induced in Wister rats through the intraperitoneal administration of STZ (50 mg/kg b.w.). Antihyperlipidemic activities of β-carotene were evaluated by oral dose (10 mg/70 kg b.w.) once daily for 21 days. Metformin (12.1 mg/kg b.w.) was used as a positive control.

Results: Blood samples of rats were drawn by tail vein puncture and cardiac puncture to determine the fasting blood glucose (FBG) and serum level of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), respectively. The result of individual treatment of β-carotene and metformin significantly (p<0.001) reversed the diabetes induced increase in FBG, LDL, TC and TG, whereas pointedly increased the STZ-induced decrease in HDL, if compared to the diabetic control.

Conclusion: The monotherapy of β-carotene had important antidiabetic and antihyperlipidemic effects and provided a scientific rationale for their use in antidiabetic therapy as a potential antioxidant.

Keywords: Diabetes mellitus, antihyperglycemic, antihyperlipidemic, metformin, β-carotene


How to Cite

Khanam, K., Mostofa Kamal, A. H. M., Yeasmin, M. and Rajia, S. (2022) “Antidiabetic and Antihyperlipidemic Activity of β-carotene on Streptozotocin-induced Diabetic Rats”, Journal of Pharmaceutical Research International, 34(62), pp. 36–44. doi: 10.9734/jpri/2022/v34i627283.

Downloads

Download data is not yet available.

References

Shete V, Quadro L. Mammalian metabolism of β-carotene: gaps in knowledge. Nutrients. 2013;5(12):4849-68.

DOI: 10.3390/nu5124849

Mounien L, Tourniaire F, Landrier JF. Anti-Obesity Effect of Carotenoids: Direct Impact on Adipose Tissue and Adipose Tissue-Driven Indirect Effects. Nutrients. 2019;11 (7):1562.

DOI: 10.3390/nu11071562

Rodriguez-Concepcion M, Avalos J, Bonet ML, Boronat A, Gomez-Gomez L, Hornero-Mendez D, Limon MC, Meléndez-Martínez AJ, Olmedilla-Alonso B, Palou A, Ribot J, Rodrigo MJ, Zacarias L, Zhu C. A global perspective on carotenoids: Metabolism, biotechnology, and benefits for nutrition and health. Prog Lipid Res. 2018;70:62-93.

DOI: 10.1016/j.plipres.2018.04.004

Conrad O. Perera, Gan Mei Yen, Functional Properties of Carotenoids in Human Health, International Journal of Food Properties. 2007; 10:2, 201- 230.

DOI: 10.1080/10942910601045271

Patel DK, Kumar R, Prasad SK, Sairam K, Hemalatha S. Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed. 2011;1(4):316-22.

DOI: 10.1016/S2221-1691(11)60051-8

Li WL, Zheng HC, Bukuru J,De Kimpe N. Natural medicines used in traditional Chinese medical system for therapy of diabetic mellitus. J. Ethnopharmacol. 2004;92:1-21.

Sy GY, Cissé A, Nongonierma RB, Sarr M, Mbodj NA, Faye B. Hypoglycaemic and antidiabetic activity of acetonic extract of Vernonia colorata leaves in normoglycaemic and alloxan-induced diabetic rats. J Ethnopharmacol. 2005; 98(1-2):171-5.

Web World Health Rankings. Bangladesh: Diabetes Mellitus.

Available:https://www.worldlifeexpectancy.com/ bangladesh-diabetes-mellitus

[Last accessed on 10 Apr 2021]

Basha B, Samuel SM, Triggle CR, and Ding H. Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?. Exp Diabetes Res. 2012; 2012:481840.

O'Brien T, Nguyen TT, Zimmerman BR. Hyperlipidemia and diabetes mellitus. Mayo Clin Proc. 1998;73(10): 969-76.

DOI: 10.4065/73.10.969

Beladi Mousavi SS, Nasri H, Rafieian-Kopaei M, Tamadon MR. Metformin improves diabetic kidney disease. J Nephropharmacol. 2012;1(1):1-2.

Ayodhya S, Kusum S, Saxena A. Hypoglycaemic activity of different extracts of various herbal plants. Int J Res Ayurveda Pharm. 2010;1:212.

Abdollahi M, Farshchi A, Nikfar S, Seyedifar M. Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials. J Pharm Pharm Sci. 2013;16(1):99-114.

DOI: 10.18433/j3g022

Rafieian-Kopaei M, Nasri H. Ginger and diabetic nephropathy. J Renal Inj Prev. 2013;2(1):9-10.

DOI: 10.12861/jrip.2013.05

Nasri H, Rafieian-Kopaei M. Tubular Kidney Protection by Antioxidants. Iran J Public Health. 2013;42(10):1194-6.

Ardalan MR, Sanadgol H, Nasri H, Baradaran A, Tamadon MR, Rafieian-Kopaei R. Vitamin D therapy in diabetic kidney disease; current knowledge on a public health problem. J Parathyr Dis. 2014;2:15-7.

Basha B, Samuel SM, Triggle CR, Ding H. Endothelial dysfunction in diabetes mellitus: possible involvement of endoplasmic reticulum stress?. Exp Diabetes Res. 2012;481840.

DOI: 10.1155/2012/481840

Rojas LB, Gomes MB. Metformin: an old but still the best treatment for type 2 diabetes. Diabetol Metab Syndr. 2013; 5(1):6.

DOI: 10.1186/1758-5996-5-6

Namitha KK, Negi PS. Chemistry and biotechnology of carotenoids. Crit Rev Food Sci Nutr. 2010;50(8):728-60.

DOI: 10.1080/10408398.2010.499811

Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and disease. Nutrients. 2014;6(2): 466-88.

DOI: 10.3390/nu6020466

Roy P, Islam M, Islam MS, Rashid M. Beneficial Effects of Combination Therapy of Sitagliptin and β-carotene Drugs on Streptozotocin-induced Diabetic Rats. Bangladesh Pharm J. 2020;23:87-95.

Guide for the Care and Use of Laboratory Animals. 8th Edition. Washington DC: The National Academies Press; 2011.

Zannah S, Islam M, Ali Y, Asaduzzaman M, Sarwar MS, Al Bari AA, Rashid M. Antidiabetics in Combination with Hydroxychloroquine Improve Antioxidant and Hepatoprotective Activities in Alloxan- Induced Diabetic Rats. Bangladesh pharm J. 2015;18:72-77.

Ira J. Goldberg. Diabetic Dyslipidemia: Causes and Consequences. J. Clin. Endocrinol. Metab. 2001;86(1):965–971.

Available:https://doi.org/10.1210/jcem.86.3.7304.

Viollet B, Guigas B, Garcia NS, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012;122: 253-70.

Minamii T, Nogami M, Ogawa W. Mechanisms of metformin action: In and out of the gut. J Diabetes Investig. 2018;9:701-703.

Yang J, Holman GD. Long-term metformin treatment stimulates cardiomyocyte glucose transport through an AMP-activated protein kinase-dependent reduction in GLUT4 endocytosis. Endocrinology. 2006;147:2728-36.

Sharma AK, Raikwar SK, Kurmi MK, Srinivasan BP. Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats. Inflammopharmacology. 2013;21(2): 137-45.

DOI: 10.1007/s10787-012-0154-4

Ghosal S and Ghosal S. The Side Effects of Metformin - A Review. J Diabetes Metab Disord. 2019; 6 030.

DOI: 10.24966/DMD-201X/100030.

Khanam K, Rajia S, Yeasmin M, Morshed M, and Haque R. Synergistic Effect of β-Carotene and Metformin on Antihyperglycemic and Antidyslipidemic Activities in Streptozotocin-Induced Diabetic Rats. J. Pharm. Res. Int. 2021; 33(51A):79-87.

DOI: 10.9734/jpri/2021/v33i51A33471

Ruhe RC, McDonald RB. Use of Antioxidant Nutrients in the Prevention and Treatment of Type 2 Diabetes. J Am Coll Nutr. 2001;20:363S-9.

Sharma A, Chand T, Khardiya M, Yadav KC, Mangal R, Sharma AK, Antidiabetic and Antihyperlipidemic Activity of Annona Squamosa Fruit Peel in Streptozotocin Induced Diabetic Rats. IJPTR. 2013; 5(1):15-21.

Rajia S, Khanam K, Farhana U, Rahman S, Haque R. Piper Chaba Extracts With Antibiofilm Activity Influence Antihyperglycemic And Antihyperlipidemic Responses In Diabetic Wister Rats. Int J Pharm Pharm Sci [Internet]. 2021;13(9): 44-9.

Sharma A, Sharma AK, Chand T, Khardiya M, Yadav KC. Antidiabetic and Antihyperlipidemic Activity of Cucurbita maxima Duchense (Pumpkin) Seeds on Streptozotocin Induced Diabetic Rats. RJPP. 2013;1(6):108-116.

Amengual J, Gouranton E, Helden YGJ, Hessel S, Ribot J, Kramer E, Kiec-Wilk B, Razny U, Lietz A, Wyss A, et al. Beta-carotene reduces body adiposity of mice via BCMO1. PLoS ONE. 2011;6:e20644.

Beydoun MA, Chen X, Jha K, Beydoun HA, Zonderman AB, Canas JA. Carotenoids, vitamin A, and their association with the metabolic syndrome: A systematic review and meta-analysis. Nutr. Rev. 2019;77:32–45.

Canas JA, Lochrie A, McGowan AG, Hossain J, Schettino C, Balagopal PB. Effects of mixed carotenoids on adipokines and abdominal adiposity in children: A pilot study. J. Clin. Endocrinol. Metab. 2017;102:1983–1990.

Asemi Z, Alizadeh SA, Ahmad K, Goli M, Esmailzadeh A. Effects of beta-carotene fortified symbiotic food on metabolic control of patients with type 2 diabetes mellitus: A double-blind randomized cross-over controlled clinical trial. Clin. Nutr. 2016;35:819–825.

Szuszkiewicz-Garcia MM, Davidson JA. Cardiovascular disease in diabetes mellitus: Risk factors and medical therapy. Endocrinol Metab Clin of N Am. 2014;43:25-40.

Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008;358(20):2148-59.

DOI: 10.1056/NEJMra0800239

Kasperczyk S,Dobrakowski M, Kasperczyk J, Ostałowska A, Zalejska-Fiolka J, Birkner E. Beta-carotene reduces oxidative stress, improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers. Toxicology and Applied Pharmacology. 2014;280:36- 41.

Canas JA, Lochrie A, McGowan AG, Hossain J, Schettino C, Balagopal PB. Effects of mixed carotenoids on adipokines and abdominal adiposity in children: A pilot study. J. Clin. Endocrinol. Metab. 2017; 102:1983–1990.

DOI: 10.1210/jc.2017-00185

Canas JC, Damaso L, Altamare A, Killen K, Hossain J, Balagopal PB. Insulin resistance and adiposity in relation to serum β-carotene levels. J. Pediatr. 2012; 161:58–64.

DOI: 10.1016/j.jpeds.2012.01.030

Furusho T, Kataoka E, Yasuhara T, Wada M, Innami S. Administration of betacarotene suppresses lipid peroxidation in tissues and improves the glucose tolerance ability of streptozotocin-induced diabetic rats. Int J Vitam Nutr Res. 2002;72:71-6.

Roohbakhsh A, Karimi G, Iranshahi M. Carotenoids in the treatment of diabetes mellitus and its complications: a mechanistic review. Biomed Pharmacother. 2017;91:31-42.

Fathalipour M, Fathalipour H, Safa O, Nowrouzi-Sohrabi P, Mirkhani H, Hassanipour S. The Therapeutic Role of Carotenoids in Diabetic Retinopathy: A Systematic Review. Diabetes Metab Syndr Obes. 2020;13:2347-2358.

DOI: 10.2147/DMSO.S255783

Gammone MA, Pluchinotta FR, Bergante S, Tettamanti G, D’Orazio N. Prevention of cardiovascular diseases with carotenoids. Front Biosci. 2017;9: 165-71.

Seo JS, Lee KS, Jang HJ, Quan Z, Yang KM, Burri BJ. The effect of dietary supplementation of β-carotene on lipid metabolism in streptozotocin-induced diabetic rats. Nutr Res. 2004;24: 1011- 21.