Synergetic Effect of Lupeol and Naringin Against Bile Duct Ligation Induced Cardiac Injury in Rats via Modulating Nitrite Level (eNos) and NF-kB /p65 Expression

Abstract

Cardiac dysfunction such as cirrhotic cardiomyopathy is more common in liver cirrhosis related disorders including primary biliary cholangitis or biliary cirrhosis and primary sclerosing cholangitis. Bile duct ligation (BDL) is an effective model of biliary cholestasis, producing oxidative damage and fibrosis. This research was designed to evaluate the effect of Lupeol and Naringin and its combination on bile duct ligation induced cardiac injury in rats. For pharmacological evaluation, rats were randomly divided into seven groups; intrahepatic cholestasis induced by ligation of the bile duct might lead to cirrhotic cardiomyopathy. The results were analyzed by physical, biochemical and histological examination. The Lupeol (100 mg/kg, p.o.), Naringin (100 mg/kg, p.o.) and its combination (100 mg/kg each) treated group significantly improved physical infarct size, biochemical (Nitrite, SOD, CAT, and GSH) and histological (heart tissue- mitochondrial function/integrity and fibrosis) alterations occurs due to BDL-ligation. This study was concluded that oral administration of Lupeol, Naringin, and its combination has a curative potential against BDL-induced cardiac injury in rats by reducing oxidative stress and inflammatory reactions, resulting in reduced heart necrosis/myocardial infarction and increased myocardial activity. It also inhibits cardiac damage in the rat heart, these effects may be linked to the NO level (eNOS) is increased and the inactivation of the NF-kB-p65 expression pathways.This study also provides new insights into the development of lupeol and Naringin combination that can be used as supportive therapy for cardiovascular diseases.

Keywords

Bile duct ligation - Lupeol - Naringin - cardiomyopathy - NF-kB-p65 expression.

Publication History

Received: 19 May 2022

Accepted: 20 June 2022

Article published online:
22 September 2022

• References

• 1 Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, Vinicor F. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107: 499-511
• 2 Møller S, Henriksen J. H. Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects. In Seminars in nephrology 1997; 17: 505-519
• 3 Han X, Shen T, Lou H. Dietary polyphenols and their biological significance. International journal of molecular sciences 2007; 8: 950-988
• 4 Liu ZC, Meng LQ, Song JH, Gao J. Dynamic protein expression of NF-κB following rat intracerebral hemorrhage and its association with apoptosis. Experimental and Therapeutic Medicine 2018; 16: 3903-3908
• 5 Rangaswami S, Seshadri TR, Veeraraghava J. Constitution of naringin. In Proceedings of the Indian Academy of Sciences-Section A 1939; 9, No. 4 328-332
• 6 Ovesna Z, Vachalkova A, Horvathova K, Tothova D. Pentacyclic triterpenoic acids: new chemoprotective compounds Minireview. Neoplasma 2004; 51: 327-333
• 7 Tokaç M, Taner G, Aydın S, Özkardeş AB, Dündar HZ, Taşlıpınar MY, Basaran N. Protective effects of curcumin against oxidative stress parameters and DNA damage in the livers and kidneys of rats with biliary obstruction. Food and Chemical Toxicology 2013; 61: 28-35
• 8 Aller MA, Arias JL, García-Domínguez J, Arias JI, Durán M, Arias J. Experimental obstructive cholestasis: the wound-like inflammatory liver response. Fibrogenesis & tissue repair 2008; 1: 1-17
• 9 Panda S, Kar A, Banerjee T, Sharma N. Combined effects of quercetin and atenolol in reducing isoproterenol-induced cardiotoxicity in rats: possible mediation through scavenging free radicals. Cardiovascular Toxicology 2012; 12: 235-242
• 10 Anchi P, Khurana A, Bale S, Godugu C. The role of plant-derived products in pancreatitis: experimental and clinical evidence. Phytotherapy Research 2017; 31: 591-623
• 11 Karthikeyan K, Bai BS, Devaraj SN. Efficacy of grape seed proanthocyanidins on cardioprotection during isoproterenol-induced myocardial injury in rats. Journal of cardiovascular pharmacology 2009; 53: 109-115
• 12 Rzucidlo SJ. Influences of glutathione on embryo quality and acetaminophen toxicity in a novel transgenic mouse model . University of Georgia. 1998
• 13 Zanwar AA, Hegde MV, Bodhankar SL. Cardioprotective activity of flax lignan concentrate extracted from seeds of Linum usitatissimum in isoprenaline induced myocardial necrosis in rats. Interdisciplinary toxicology 2011; 4: 90
• 14 Davidson SM, Adameová A, Barile L, Cabrera-Fuentes HA, Lazou A. , Pagliaro. Mitochondrial and mitochondrial-independent pathways of myocardial cell death during ischaemia and reperfusion injury. Journal of Cellular and Molecular Medicine 2020; 24: 3795-3806
• 15 Liu ZC, Meng LQ, Song JH, Gao J. Dynamic protein expression of NF-κB following rat intracerebral hemorrhage and its association with apoptosis. Experimental and Therapeutic Medicine 2018; 16: 3903-3908
• 16 Viswanatha GL, Shylaja H, Moolemath Y. The beneficial role of Naringin-a citrus bioflavonoid, against oxidative stress-induced neurobehavioral disorders and cognitive dysfunction in rodents: A systematic review and meta-analysis. Biomedicine & Pharmacotherapy 2017; 94: 909-929
• 17 Abbasi A, Faramarzi N, Khosravi M, Yazarloo F, Abbasi MA, Dehpour AR. , & Jahanzad. Fas receptor activation by endogenous opioids is A new mechanism for cardiomyopathy in cirrhotic rats. Journal of clinical and experimental hepatology 2017; 7: 107-114
• 18 Zhang S, Zhang Y. Isoflurane reduces endotoxin-induced oxidative, inflammatory, and apoptotic responses in H9c2 cardiomyocytes. Eur Rev Med Pharmacol Sci 2018; 22: 3976-3987