Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.
Hossain, P.; Kawar, B.; El Nahas, M. Obesity and diabetes in the developing world—a growing challenge. N. Eng. J. Med. 2007, 356, 213–215, doi:10.1056/NEJMp068177.
Phillips, L.; Prins, J. The link between abdominal obesity and the metabolic syndrome. Curr. Hypertens. Rep. 2008, 10, 156–164, doi:10.1007/s11906-008-0029-7.
Jeon, S.M.; Park, Y.B.; Choi, M.S. Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits. Clin. Nutr. 2004, 23, 1025–1034, doi:10.1016/j.clnu.2004.01.006.
Rajadurai, M.; Prince, P.S.M. Preventive effect of naringin on lipids, lipoproteins and lipid metabolic enzymes in isoproterenol-induced myocardial infarction in Wistar rats. J. Biochem. Mol. Toxicol. 2006, 20, 191–197, doi:10.1002/jbt.20136.
Rajadurai, M.; Prince, P.S.M. Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: Biochemical and histopathological evidences. Toxicology 2006, 228, 259–268, doi:10.1016/j.tox.2006.09.005.
Kannappan, S.; Anuradha, C.V. Naringenin enhances insulin-stimulated tyrosine phosphorylation and improves the cellular actions of insulin in a dietary model of metabolic syndrome. Eur. J. Nutr. 2010, 49, 101–109, doi:10.1007/s00394-009-0054-6.
Sharma, A.K.; Bharti, S.; Ojha, S.; Bhatia, J.; Kumar, N.; Ray, R.; Kumari, S.; Arya, D.S. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br. J. Nutr. 2011, 106, 1713–1723, doi:10.1017/S000711451100225X.
Jung, U.J.; Lee, M.K.; Park, Y.B.; Kang, M.A.; Choi, M.S. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int. J. Biochem. Cell. Biol. 2006, 38, 1134–1145, doi:10.1016/j.biocel.2005.12.002.
Panchal, S.K.; Poudyal, H.; Brown, L. Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. J. Nutr. 2012, 142, 1026–1032, doi:10.3945/jn.111.157263.
Panchal, S.K.; Poudyal, H.; Waanders, J.; Brown, L. Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J. Nutr. 2012, 142, 690–697, doi:10.3945/jn.111.153577.
Niehius, W.G.; Samuelsson, B. Formation of malondialdehyde from phospholipids arachidonate during microsomal lipidperoxidation. Eur. J. Biochem. 1968, 6, 126–130, doi:10.1111/j.1432-1033.1968.tb00428.x.
Chanet, A.; Milenkovic, D.; Manach, C.; Mazur, A.; Morand, C. Citrus flavanones: What is their role in cardiovascular protection? J. Agric. Food Chem. 2012, 60, 8809–8822.
Ikemura, M.; Sasaki, Y.; Giddings, J.C.; Yamamoto, J. Preventive effects of hesperidin, glucosyl gesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats. Phytother. Res. 2012, 26, 1272–1277, doi:10.1002/ptr.3724.
Jain, M.; Parmar, H.S. Evaluation of antioxidative and anti-inflammatory potential of hesperidin and naringin on the rat air pouch model of inflammation. Inflamm. Res. 2011, 60, 483–491, doi:10.1007/s00011-010-0295-0.
Morikawa, K.; Nonaka, M.; Mochizuki, H.; Handa, K.; Hanada, H.; Hirota, K. Naringenin and hesperetin induce growth arrest, apoptosis, and cytoplasmic fat deposit in human preadipocytes. J. Agric. Food Chem. 2008, 26, 11030–11037.
Jung, U.J.; Lee, M.K.; Jeong, K.S.; Choi, M.S. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J. Nutr. 2004, 134, 2499–2503.
Parmer, H.S.; Jain, P.; Chauhan, D.S.; Bhinchar, M.K.; Munjal, V.; Yusuf, M.; Choube, K.; Tawani, A.; Tiwari, V.; Manivannan, E.; Kumar, A. DPP-IV inhibitory potential of naringin: An in silico, in vitro and in vivo study. Diabetes Res. Clin. Pract. 2012, 97, 105–111, doi:10.1016/j.diabres.2012.02.011.
Kim, S.-Y.; Kim, H.-J.; Lee, M.-K.; Jeon, S.-M.; Do, G.-M.; Kwon, E.-Y.; Cho, Y.Y.; Kim, D.J.; Jeong, K.S.; Park, Y.B.; et al. Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet. J. Med. Food 2006, 9, 582–586, doi:10.1089/jmf.2006.9.582.
Demonty, I.; Lin, Y.; Zebregs, Y.E.; Vermeer, M.A.; van der Knaap, H.C.; Jaekel, M.; Trautwein, E.A. The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J. Nutr. 2010, 140, 1615–1620, doi:10.3945/jn.110.124735.
Ali, M.M.; El Kader, M.A. The influence of naringin on the oxidative state of rats with streptozotocin-induced acute hyperglycaemia. Z. Naturforsch. C 2004, 59, 726–733.
Crespy, V.; Morand, C.; Besson, C.; Cotelle, N.; Vezin, H.; Demigne, C.; Remesy, C. The splanchnic metabolism of flavonoids highly differed according to the nature of the compound. Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 284, G980–G988.
Bokkenheuser, V.D.; Shackleton, C.H.; Winter, J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans. Biochem. J. 1987, 248, 953–956.
Erlund, I.; Meririnne, E.; Alfthan, G.; Aro, A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J. Nutr. 2001, 131, 235–241.
Kanaze, F.I.; Bounartzi, M.I.; Georgarakis, M.; Niopas, I. Pharmacokinetics of the citrus flavonone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur. J. Clin. Nutr. 2007, 61, 472–477.
Vajro, P.; Paolella, G.; Fasano, A. Microbiota and gut-liver axis: A mini-review on their influence on obesity and obesity related liver disease. J. Pediatr. Gastroenterol. Nutr. 2013, doi:10.1097/MPG.0b013e318284abb5.
Bolca, S.; van de Wiele, T.; Possemiers, S. Gut metabotypes govern health effects of dietary polyphenols. Curr. Opin. Biotechnol. 2012, doi:10.1016/j.copbio.2012.09.009.
Tuohy, K.M.; Conferno, L.; Gasperotti, M.; Viola, R. Up-regulating the human intestinal microbiome using whole plant foods, polyphenols, and/or fiber. J. Agric. Food Chem. 2012, 60, 8776–8782, doi:10.1021/jf2053959.
Bachmann, K.; Pardoe, D.; White, D. Scaling basic toxicokinetic parameters from rat to man. Environ. Health Perspect. 1996, 104, 400–407, doi:10.1289/ehp.96104400.
