Abstract
In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100 mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.
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References
Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Saturated fat, carbohydrate, and cardiovascular disease. Am J Clin Nutr. 2010;91:502–9.
Wali JA, Jarzebska N, Raubenheimer D, Simpson SJ, Rodionov RN, O’Sullivan JF. Cardio-metabolic effects of high-fat diets and their underlying mechanisms-a narrative review. Nutrients. 2020;12:1505.
Alves-Bezerra M, Cohen DE. Triglyceride metabolism in the liver. Compr Physiol. 2017;8:1–8.
Levitan I, Volkov S, Subbaiah PV. Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid Redox Signal. 2010;13:39–75.
Jump DB, Tripathy S, Depner CM. Fatty acid-regulated transcription factors in the liver. Annu Rev Nutr. 2013;33:249–69.
Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications–a review. Nutr J. 2014;13:17.
Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122:4–22.
Tan BL, Norhaizan ME. Effect of high-fat diets on oxidative stress, cellular inflammatory response and cognitive function. Nutrients. 2019;11:2579.
Safitri N, Alaina MF, Pitaloka DAE, Abdulah R. A narrative review of statin-induced rhabdomyolysis: molecular mechanism, risk factors, and management. Drug Healthc Patient Saf. 2021;13:211–9.
Shaito A, Thuan DTB, Phu HT, Nguyen THD, Hasan H, Halabi S, et al. Herbal medicine for cardiovascular diseases: efficacy, mechanisms, and safety. Front Pharmacol. 2020;11:422.
Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Medicines. 2018;5:93.
Kumar R, Rizvi SI. Vitamin C improves inflammatory-related redox status in hyperlipidemic rats. Ind J Clin Biochem. 2022. https://doi.org/10.1007/s12291-022-01070-8.
Cheng Y-C, Sheen J-M, Hu WL, Hung Y-C. Polyphenols and oxidative stress in atherosclerosis-related ischemic heart disease and stroke. Oxid Med Cell Longev. 2017;2017:8526438.
Pyrzynska K. Hesperidin: a review on extraction methods, stability and biological activities. Nutrients. 2022;14:2387.
Sengupta P. The laboratory rat: relating its age with human’s. Int J Prev Med. 2013;4:624–30.
Kumar R, Akhtar F, Rizvi SI. Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidaemic model of rat. Clin Exp Pharmacol Physiol. 2020;47:571–82.
Becker JB, Prendergast BJ, Liang JW. Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol Sex Differ. 2016;7:34.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–75.
Schnitzer E, Pinchuk I, Bor A, Fainaru M, Samuni AM, Lichtenberg D. Lipid oxidation in unfractionated serum and plasma. Chem Phys Lipids. 1998;92:151–70.
Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN. Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol. 1999;19:330–5.
Mehdi MM, Rizvi SI. Human plasma paraoxonase 1 (PON1) arylesterase activity during aging: correlation with susceptibility of LDL oxidation. Arch Med Res. 2012;43:438–43.
Ellulu MS, Patimah I, Khazaai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017;13:851–63.
Mohammadi M, Ramezani-Jolfaie N, Lorzadeh E, Khoshbakht Y, Salehi-Abargouei A. Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials. Phytother Res. 2019;33:534–45.
Demonty I, Lin Y, Zebregs YEMP, Vermeer MA, van der Knaap HCM, Jäkel M, et al. The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J Nutr. 2010;140:1615–20.
Tabeshpour J, Hosseinzadeh H, Hashemzaei M, Karimi G. A review of the hepatoprotective effects of hesperidin, a flavanon glycoside in citrus fruits, against natural and chemical toxicities. Daru. 2020;28:305–17.
Morris G, Walker AJ, Walder K, Berk M, Marx W, Carvalho AF, et al. Increasing Nrf2 activity as a treatment approach in neuropsychiatry. Mol Neurobiol. 2021;58:2158–82.
Aja PM, Ekpono EU, Awoke JN, Famurewa AC, Izekwe FI, Okoro EJ, et al. Hesperidin ameliorates hepatic dysfunction and dyslipidemia in male Wistar rats exposed to cadmium chloride. Toxicol Rep. 2020;7:1331–8.
Jung UJ, Lee M-K, Park YB, Kang MA, 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;38:1134–45.
Grande F, Occhiuzzi MA, Perri MR, Ioele G, Rizzuti B, Statti G, et al. Polyphenols from citrus Tacle® extract endowed with HMGCR inhibitory activity: an antihypercholesterolemia natural remedy. Molecules. 2021;26:5718.
Cakatay U, Kayali R, Uzun H. Relation of plasma protein oxidation parameters and paraoxonase activity in the ageing population. Clin Exp Med. 2008;8:51–7.
Roy PK, Islam J, Lalhlenmawia H. Prospects of potential adipokines as therapeutic agents in obesity-linked atherogenic dyslipidemia and insulin resistance. Egypt Heart J. 2023;75:24.
Vergeer M, Holleboom AG, Kastelein JJP, Kuivenhoven JA. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J Lipid Res. 2010;51:2058–73.
Paz-Filho G, Mastronardi C, Wong M-L, Licinio J. Leptin therapy, insulin sensitivity, and glucose homeostasis. Indian J Endocrinol Metab. 2012;16:S549-555.
Jürimäe T, Sudi K, Jürimäe J, Payerl D, Rüütel K. Relationships between plasma leptin levels and body composition parameters measured by different methods in postmenopausal women: leptin level and body composition in women. Am J Hum Biol. 2003;15:628–36.
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Kumar, R., Khan, M.I., Ashfaq, F. et al. Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia. Ind J Clin Biochem 39, 257–263 (2024). https://doi.org/10.1007/s12291-023-01140-5
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DOI: https://doi.org/10.1007/s12291-023-01140-5