Abstract
Hyperglycemia is one of the metabolic and homeostatic abnormalities that increase the cardiovascular mortality in diabetic patients by increased oxidative stress. We have recently reported amelioration of oxidative stress in cardiac tissue by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in streptozotocin-induced diabetic rats. The mechanistic aspects of the cardio-protective influence of dietary fenugreek seeds (10%) and onion (3% powder) both individually and in combination on hyperglycemia-mediated cardiac damage was further investigated in this study on streptozotocin-induced diabetic rats. Cardio-protective influence of these dietary spices was evidenced by their blocking potential on renin–angiotensin system. This might be the consequence of reduced activation of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1) in cardiac tissue. The combination produced an additive effect on ACE and AT1 protein and mRNA expressions. Increased expression of type IV collagen, fibronectin, Bax, 4-hydroxynonenal, iNOS and metabolites of nitric oxide (nitrate/nitrite) along with disturbed PUFA-to-SFA ratio and activities of cardiac marker enzymes in blood confirmed the myocardial damage. Dietary fenugreek seed, onion and fenugreek + onion were found to ameliorate these pathological changes in the cardiovascular system. The beneficial effect being higher with the combination sometime amounting to additive (iNOS expression) or even a synergistic (cardiac Bax and type IV collagen expression and circulatory marker enzymes) in diabetic rats. Thus, the results of present investigation suggested that the combination of fenugreek seeds and onion offers higher beneficial influence in ameliorating cardiac damage accompanying diabetes.
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References
Buse, J. B., Ginsberg, H. N., Bakris, G. L., Clark, N. G., Costa, F., Eckel, R., et al. (2007). Primary prevention of cardiovascular diseases in people with diabetes mellitus a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care, 30, 162–172.
Fang, Z. Y., Prins, J. B., & Marwick, T. H. (2004). Diabetic cardiomyopathy: Evidence, mechanisms, and therapeutic implications. Endocrinology Reviews, 25, 543–567.
Murça, T. M., Moraes, P. L., Capuruço, C. A., Santos, S. H., Melo, M. B., Santos, R. A., et al. (2012). Oral administration of an angiotensin-converting enzyme 2 activator ameliorates diabetes-induced cardiac dysfunction. Regulatory Peptides, 177, 107–115.
Srinivasan, K. (2006). Fenugreek (Trigonella foenum-graecum): A review of health beneficial physiological effects. Food Reviews International, 22, 203–224.
Suleria, H. A. R., Butt, M. S., Anjum, F. M., Saeed, F., & Khalid, N. (2015). Onion: Nature protection against physiological threats. Critical Reviews in Food Science and Nutrition, 55, 50–66.
Babu, P. S., & Srinivasan, K. (1997). Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus. Molecular and Cellular Biochemistry, 175, 49–57.
Ravikumar, P., & Anuradha, C. V. (1999). Effect of fenugreek seeds on blood lipid peroxidation and antioxidants in diabetic rats. Phytotherapy Research, 13, 197–201.
Pradeep, S. R., & Srinivasan, K. (2017). Amelioration of hyperglycemia and associated metabolic abnormalities by a combination of fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in experimental diabetes. Journal of Basic and Clinical Physiology and Pharmacology, 28, 493–505.
Pradeep, S. R., & Srinivasan, K. (2017). Amelioration of oxidative stress by dietary fenugreek (Trigonella foenum-graecum) seeds is potentiated by onion (Allium cepa) in streptozotocin-induced diabetic rats. Applied Physiology, Nutrition and Metabolism, 42, 816–828.
Huggett, A. S. G., & Nixon, D. A. (1957). Use of glucose oxidase, peroxidase, and O dianisidine in determination of blood and urinary glucose. The Lancet, 270, 368–370.
Bergmeyer, H. U., & Bernt, E. (1974). LDH – UV assay with pyruvate and NADH. In H. U. Bergmeyer (Ed.), Methods of Enzymatic Analysis (Vol. 2, pp. 574–579). New York: Academic Press.
Bergmeyer, H. U., & Bernt, E. (1974). Glutamate-oxaloacetate transaminase. In H. U. Bergmeyer (Ed.), Methods of Enzymatic Analysis (Vol. 2, pp. 727–733). New York: Academic Press.
Walter, K., & Schult, C. (1974). Acid and alkaline phosphatase in serum. In H. U. Bergmeyer (Ed.), Methods of Enzymatic Analysis (Vol. 2, pp. 356–360). New York: Academic Press.
Cushman, D. W., & Cheung, H. S. (1971). Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochemical Pharmacology, 20, 1637–1648.
Folch, J., Lees, M., & Sloane-Stanley, G. H. (1957). A simple method for the isolation and purification of total lipids from animal tissues. Journal of Biochemistry, 226, 497–509.
Hajar, R. (2016). Framingham contribution to cardiovascular disease. Heart Views: The Official Journal of the Gulf Heart Association, 17, 78.
Kumar, P., Bhandari, U., & Jamadagni, S. (2014). Fenugreek seed extract inhibits fat accumulation and ameliorates dyslipidemia in high fat diet-induced obese rats. BioMed Research International. https://doi.org/10.1155/2014/606021.
Vazquez-Prieto, M. A., Rodriguez Lanzi, C., Lembo, C., Galmarini, C. R., & Miatello, R. M. (2011). Garlic and onion attenuates vascular inflammation and oxidative stress in fructose-fed rats. Journal of Nutrition and Metabolism. https://doi.org/10.1155/2011/475216.
Olayeriju, O. S., Olaleye, M. T., Crown, O. O., Komolafe, K., Boligon, A. A., Athayde, M. L., et al. (2015). Ethylacetate extract of red onion (Allium cepa L.) tunic affects hemodynamic parameters in rats. Food Science and Human Wellness, 4, 115–122.
Qiao, W., Wang, C., Chen, B., Zhang, F., Liu, Y., Lu, Q., et al. (2015). Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced diabetic rats. Cardiology, 131, 97–106.
Ozmutlu, S., Dede, S., & Ceylan, E. (2012). The effect of lycopene treatment on ACE activity in rats with experimental diabetes. Journal of Renin-Angiotensin-Aldosterone System, 13, 328–333.
Hu, J., Miyatake, F., Aizu, Y., Nakagawa, H., Nakamura, S., Tamaoka, A., et al. (1999). Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population. Neuroscience Letters, 277, 65–67.
Ustundag, B., Mehmet, Ç. A. Y., Ozercan, İ. H., Naziroglu, M., & İlhan, N. (1998). Angiotensin converting enzyme activity in the serum, lung, liver and kidney in streptozotocin-induced diabetic rats and diabetic nephropathy. Turkish Journal of Medical Science, 28, 231–238.
Bor, M. V., Elmali, E. S., & Altan, N. (2000). Serum antiotensin converting enzyme activity in streptozotocin-induced diabetic rats. Turkish Journal of Medical Science, 30, 311–314.
Ban, C. R., & Twigg, S. M. (2008). Fibrosis in diabetes complications: Pathogenic mechanisms and circulating and urinary markers. Vascular Health and Risk Management, 4, 575–596.
McKarns, S. C., & Schwartz, R. H. (2005). Distinct effects of TGF-β1 on CD4+ and CD8+ T cell survival, division, and IL-2 production: a role for T cell intrinsic Smad3. Journal of Immunology, 174, 2071–2083.
Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., & Nagata, S. (1998). A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 391, 43–50.
Naseem, K. M. (2005). The role of nitric oxide in cardiovascular diseases. Molecular Aspects of Medicine, 26, 33–65.
Nagareddy, P. R., Xia, Z., McNeill, J. H., & MacLeod, K. M. (2005). Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes. American Journal of Physiology Heart and Circulatory Physiology, 289, H2144–H2152.
Farhangkhoee, H., Khan, Z. A., Chen, S., & Chakrabarti, S. (2006). Differential effects of curcumin on vasoactive factors in the diabetic rat heart. Nutrition and Metabolism, 3, 27.
Xu, X., Xiao, H., Zhao, J., & Zhao, T. (2012). Cardioprotective effect of sodium ferulate in diabetic rats. International Journal of Medical Sciences, 9, 291–300.
Savu, O., Iosif, L., Bradescu, O. M., Serafinceanu, C., Papacocea, R., & Stoian, I. (2015). l-arginine catabolism is driven mainly towards nitric oxide synthesis in the erythrocytes of patients with type 2 diabetes at first clinical onset. Annals of Clinical Biochemistry, 52, 135–143.
Wang, G., Li, W., Lu, X., & Zhao, X. (2011). Riboflavin alleviates cardiac failure in type I diabetic cardiomyopathy. Heart International, 6, e21.
Babu, P. S., & Srinivasan, K. (1998). Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats. Molecular and Cellular Biochemistry, 181, 87–96.
Ramsammy, L. S., Haynes, B., Josepovitz, C., & Kaloyanides, G. J. (1993). Mechanism of decreased arachidonic acid in the renal cortex of rats with diabetes mellitus. Lipids, 28, 433–439.
Liu, G., Ji, W., Huang, J., Liu, L., & Wang, Y. (2016). 4-HNE expression in diabetic rat kidneys and the protective effects of probucol. Journal of Endocrinological Investigation, 39, 865–873.
Mukthamba, P., & Srinivasan, K. (2015). Hypolipidemic influence of dietary fenugreek (Trigonella foenum-graecum) seeds and garlic (Allium sativum) in experimental myocardial infarction. Food & Function, 6, 3117–3125.
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The first author (SRP) is grateful to the Council of Scientific and Industrial Research, New Delhi, for the award of senior research fellowship. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
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Pradeep, S.R., Srinivasan, K. Alleviation of Cardiac Damage by Dietary Fenugreek (Trigonella foenum-graecum) Seeds is Potentiated by Onion (Allium cepa) in Experimental Diabetic Rats via Blocking Renin–Angiotensin System. Cardiovasc Toxicol 18, 221–231 (2018). https://doi.org/10.1007/s12012-017-9431-1
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DOI: https://doi.org/10.1007/s12012-017-9431-1