Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress

Abstract

Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin (Cucurbita moschata) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect.

Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes.

Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress.

Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia.

Key words

antioxidant - C. moschata - carbonylation - cytoprotection - diabetes - hepatoprotection

• References

• 1 Heinonen SE, Genové G, Bengtsson E. et al. Animal models of diabetic macrovascular complications: key players in the development of new therapeutic approaches. J Diabetes Res 2015; 2015: 404085
• 2 WHO . Expert committee on diabetes mellitus: second report. World Health Organ Tech Rep Ser 1980; 646: 1-80
• 3 Mirmohammadlu M, Hosseini SH, Kamalinejad M. et al. Hypolipidemic, hepatoprotective and renoprotective effects of Cydonia oblonga Mill. Fruit in streptozotocin-induced diabetic rats. Iran J Pharm Res 2015; 14: 1207-1214
• 4 Ahmadi A, Khalili M, Margedari Sh. et al. The effects of solvent polarity on hypoglycemic and hypolipidemic activities of securigera securidaca (L.) Seeds. Drug Res (Stuttg) 2016; 66: 130-135
• 5 Andrade-Cetto A, Heinrich M. Mexican plants with hypoglycaemic effect used in the treatment of diabetes. J Ethnopharmacol 2005; 99: 325-348
• 6 El-Mosallamy AE, Sleem AA, Abdel-Salam OM. et al. Antihypertensive and cardioprotective effects of pumpkin seed oil. J Med Food 2012; 15: 180-189
• 7 Hammer KA, Carson CF, Riley TV. Antimicrobial activity of essential oils and other plant extracts. J Appl Microbiol 1999; 86: 985-990
• 8 Suphakarn VS, Yarnnon C, Ngunboonsri P. The effect of pumpkin seeds on oxalcrystalluria and urinary compositions of children in hyperendemic area. Am J Clin Nutr 1987; 45: 115-121
• 9 Wang HX, Ng TB. Isolation of cucurmoschin, a novel antifungal peptide abundant in arginine, glutamate and glycine residues from black pumpkin seeds. Peptides 2003; 24: 969-972
• 10 Xie J, Que W, Liu H. et al. Anti-proliferative effects of cucurmosin on human hepatoma HepG2 cells. Mol Med Rep 2012; 5: 196-201
• 11 Yang X, Zhao Y, Lv Y. Chemical composition and antioxidant activity of an acidic polysaccharide extracted from Cucurbita moschata Duchesne ex Poiret. J Agric Food Chem 2007; 55: 4684-5690
• 12 Zhang B, Huang H, Xie J. et al. Cucurmosin induces apoptosis of BxPC-3 human pancreatic cancer cells via inactivation of the EGFR signaling pathway. Oncol Rep 2012; 27: 891-897
• 13 Zhao XH, Qian L, Yin DL. et al. Hypolipidemic effect of the polysaccharides extracted from pumpkin by cellulase-assisted method on mice. Int J Biol Macromol 2014; 64: 137-138
• 14 Jiang Z, Du Q. Glucose-lowering activity of novel tetrasaccharide glyceroglycolipids from the fruits of Cucurbita moschata. Bioorg Med Chem Lett 2011; 21: 1001-1003
• 15 Quanhong L, Caili F, Yukui R. et al. Effects of protein-bound polysaccharide isolated from pumpkin on insulin in diabetic rats. Plant Foods Hum Nutr 2005; 60: 13-16
• 16 Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010; 107: 1058-1070
• 17 Vistoli G, De Maddis D, Cipak A. et al. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation. Free Radic Res 2013; 47: 3-27
• 18 Aldini G, Dalle-Donne I, Facino RM. et al. Intervention strategies to inhibit protein carbonylation by lipoxidation-derived reactive carbonyls. Med Res Rev 2007; 27: 817-886
• 19 Banach MS, Dong Q, O’Brien PJ. Hepatocyte cytotoxicity induced by hydroperoxide (oxidative stress model) or glyoxal (carbonylation model): prevention by bioactive nut extracts or catechins. Chem Biol Interact 2009; 178: 324-331
• 20 Shahraki J, Zareh M, Kamalinejad M. et al. Cytoprotective effects of hydrophilic and lipophilic extracts of pistacia vera against oxidative versus carbonyl stress in rat hepatocytes. Iran J Pharm Res 2014; 13: 1263-1277
• 21 Gholami S, Hosseini MJ, Jafari L. et al. Mitochondria as a target for the cardioprotective effects of cydonia oblonga Mill. and Ficus carica L. in doxorubicin-induced cardiotoxicity. Drug Res (Stuttg) 2017; 67: 358-365
• 22 Eskandari MR, Pourahmad J, Daraei B. Thallium(I) and thallium(III) induce apoptosis in isolated rat hepatocytes by alterations in mitochondrial function and generation of ROS. Toxicol Environ Chem 2011; 93: 145-156
• 23 Fard JK, Hamzeiy H, Sattari M. et al. Triazole rizatriptan Induces Liver Toxicity through Lysosomal/Mitochondrial Dysfunction. Drug Res (Stuttg) 2016; 66: 470-478
• 24 Ahmadian E, Babaei H, Mohajjel Nayebi A. et al. Mechanistic approach for toxic effects of bupropion in primary rat hepatocytes. Drug Res (Stuttg) 2017; 67: 217-222
• 25 Eskandari MR, Rahmati M, Khajeamiri AR. et al. A new approach on methamphetamine-induced hepatotoxicity: involvement of mitochondrial dysfunction. Xenobiotica 2014; 44: 70-76
• 26 Eskandari MR, Mashayekhi V, Aslani M. et al. Toxicity of thallium on isolated rat liver mitochondria: the role of oxidative stress and MPT pore opening. Environ Toxicol 2015; 30: 232-241
• 27 Heidari H, Kamalinejad M, Noubarani M. et al. Protective mechanisms of Cucumis sativus in diabetes-related models of oxidative stress and carbonyl stress. Bioimpacts 2016; 6: 33-39
• 28 Novak RF, Kharasch ED, Wendel NK. Nitrofurantoin stimulated proteolysis in human erythrocytes: a novel index of toxic insult by nitroaromatics. J Pharmacol Exp Ther 1988; 247: 439-444
• 29 Eskandari MR, Moghaddam F, Shahraki J. et al. A comparison of cardiomyocyte cytotoxic mechanisms for 5-fluorouracil and its pro-drug capecitabine. Xenobiotica 2015; 45: 79-87
• 30 Dong Q, Banaich MS, O’Brien PJ. Cytoprotection by almond skin extracts or catechins of hepatocyte cytotoxicity induced by hydroperoxide (oxidative stress model) versus glyoxal or methylglyoxal (carbonylation model). Chem Biol Interact 2010; 185: 101-109
• 31 Jepsen P, Watson H, Andersen PK. et al. Diabetes as a risk factor for hepatic encephalopathy in cirrhosis patients. J Hepatol 2015; 63: 1133-1138
• 32 Koehler EM, Plompen EP, Schouten JN. et al. Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: the rotterdam study. Hepatology 2016; 63: 138-147
• 33 Chen J, Han Y, Xu C. et al. Effect of type 2 diabetes mellitus on the risk for hepatocellular carcinoma in chronic liver diseases: a meta-analysis of cohort studies. Eur J Cancer Prev 2015; 24: 89-99
• 34 Yang JD, Mohamed HA, Cvinar JL. et al. Diabetes mellitus heightens the risk of hepatocellular carcinoma except in patients with hepatitis c cirrhosis. Am J Gastroenterol 2016; 111: 1573-1580
• 35 Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999; 48: 1-9
• 36 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820
• 37 Harrison D, Griendling KK, Landmesser U. et al. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003; 91: 7A-11A
• 38 Kaneto H, Katakami N, Matsuhisa M. et al. Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators Inflamm 2010; 2010: 453892
• 39 Wright Jr E, Scism-Bacon JL, Glass LC. Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int J Clin Pract 2006; 60: 308-314
• 40 Jaswir I, Shahidan N, Othman R. et al. Effects of season and storage period on accumulation of individual carotenoids in pumpkin flesh (Cucurbita moschata). J Oleo Sci 2014; 63: 761-767
• 41 Kim MY, Kim EJ, Kim YN. et al. Comparison of the chemical compositions and nutritive values of various pumpkin (Cucurbitaceae) species and parts. Nutr Res Pract 2012; 6: 21-27
• 42 Tsai YS, Tong YC, Cheng JT. et al. Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced prostate growth in rats. Urol Int 2006; 77: 269-274