Cardioprotective effects of total and anthocyanin-rich extracts of Opuntia ficus-indica fruit on epinephrine-induced cardiac injury in rats

Abstract

Objective: To examine the effect of fruit extracts of Opuntia ficus-indica on epinephrine-induced myocardial injury in rats. Methods: Rats were pre-treated with hydroalcoholic and anthocyanin-rich extracts (250, 500, and 1 000 mg/kg) orally for 16 days. Epinephrine (2 mg/kg) was injected subcutaneously on days 15 and 16. Then ECG, heart rate, RR interval, cardiac histopathology, and serum parameters of cardiac damage and oxidative stress were evaluated. Results: Pretreatment with the hydroalcoholic and anthocyanin-rich extracts of Opuntia ficus-indica at doses of 500 and 1 000 mg/kg reversed epinephrine-induced changes in ECG, heart rate, RR interval, and cardiac histopathology, and attenuated creatine phosphokinase-MB activity and malondialdehyde level. The extracts at all doses diminished heart weight, lactate dehydrogenase, and aspartate aminotransferase, and also elevated total antioxidant capacity. However, 1 000 mg/kg of the anthocyanin-rich extract was more effective than the hydroalcoholic extract. Conclusions: Supplementation with fruit extracts of Opuntia ficus-indica, especially anthocyanin-rich extract, could protect against epinephrine-induced cardiac injury in rats by alleviating electrocardiographic, biochemical, histopathological, and oxidative stress parameters, and may be used in the treatment of cardiovascular diseases.

Keywords

Opuntia ficus-indica / Antioxidant / Cardiovascular diseases / Epinephrine / Cardiac injuries / Lipid peroxidation

Conflict of interest statement

The authors declared no conflict of interest.

Funding

This study was financially supported by Vice-Chancellery for Research and Technology of Isfahan University of Medical Sciences (research project No. 240256).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

LS was responsible for the conceptualization of the study, supervision, designing the animal investigation, and editing of the manuscript; ZH contributed to the histopathological examination; MS designed the herbal studies; MF and MK were involved in the animal treatments, data acquisition, and writing original draft.

References

[1] Al-Gahtani S, Abozaid T, Al-Gahtani S, Shoukri MM, Aleid M. Investigating trend in cardiovascular disease mortality and its association with obesity in the Gulf Cooperative Council (GCC) countries from 1990 to 2019. Open J Epidemiol 2022; 12(3): 221-230.

[2] Gabriel-Costa D. The pathophysiology of myocardial infarction-induced heart failure. Pathophysiology 2018; 25(4): 277-284.

[3] Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019; 40(3): 237-269.

[4] Neri M, Riezzo I, Pascale N, Pomara C, Turillazzi E. Ischemia/reperfusion injury following acute myocardial infarction: A critical issue for clinicians and forensic pathologists. Mediators Inflamm 2017; 2017. doi: 10.1155/2017/7018393.

[5] Perricone AJ, Vander Heide RS. Novel therapeutic strategies for ischemic heart disease. Pharmacol Res 2014; 89: 36-45.

[6] Otręba M, Kośmider L, Rzepecka-Stojko A. Polyphenols’ cardioprotective potential: Review of rat fibroblasts as well as rat and human cardiomyocyte cell lines research. Molecules 2021; 26(4): 774.

[7] Kaur M, Kaur A, Sharma R. Pharmacological actions of Opuntia ficus indica: A review . J Appl Pharm Sci 2012; 2(7): 15-18.

[8] Park EH, Kahng JH, Paek EA. Studies on the pharmacological actions of cactus: Identification of its anti-inflammatory effect. Arch Pharmacal Res 1998; 21(1): 30-34.

[9] Dok-Go H, Lee KH, Kim HJ, Lee EH, Lee J, Song YS, et al. Neuroprotective effects of antioxidative flavonoids, quercetin,(+)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. saboten . Brain Res 2003; 965(1-2): 130-136.

[10] Hwang SH, Kang IJ, Lim SS. Antidiabetic effect of fresh nopal (Opuntia ficus-indica) in low-dose streptozotocin-induced diabetic rats fed a high-fat diet . Evid Based Complement Alternat Med 2017; 2017(1). doi: 10.1155/2017/4380721.

[11] Galati EM, Tripodo MM, Trovato A, Miceli N, Monforte MT. Biological effect of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter: Note I: Diuretic activity . J Ethnopharmacol 2002; 79(1): 17-21.

[12] Akkol EK, Ilhan M, Karpuz B, Genç Y, Sobarzo-Sánchez E. Sedative and anxiolytic activities of Opuntia ficus indica (L.) Mill.: An experimental assessment in mice . Molecules 2020; 25(8): 1844.

[13] Schmitt L, Fouillot JP, Nicolet G, Midol A. Opuntia ficus indica increases heart-rate variability in high-level athletes . Int J Sport Nutr Exerc Metab 2008; 18(2): 169-178.

[14] Onakpoya IJ, O’Sullivan J, Heneghan CJ. The effect of cactus pear (Opuntia ficus-indica) on body weight and cardiovascular risk factors: A systematic review and meta-analysis of randomized clinical trials . Nutrition 2015; 31(5): 640-646.

[15] Khouloud A, Abedelmalek S, Chtourou H, Souissi N. The effect of Opuntia ficus-indica juice supplementation on oxidative stress, cardiovascular parameters, and biochemical markers following yo-yo intermittent recovery test . Food Sci Nutr 2018; 6(2): 259-268.

[16] Dhaouadi K, Raboudi F, Funez-Gomez L, Pamies D, Estevan C, Hamdaoui M, et al. Polyphenolic extract of Barbary-Fig (Opuntia ficus-indica) syrup: RP-HPLC-ESI-MS analysis and determination of antioxidant, antimicrobial and cancer-cells cytotoxic potentials . Food Anal Methods 2013; 6(1): 45-53.

[17] Zhang Y, Chang H, Shao S, Zhao L, Zhang R, Zhang S. Anthocyanins from Opuntia ficus-indica modulate gut microbiota composition and improve short-chain fatty acid production . Biology 2022; 11(10): 1505.

[18] Boukeloua AH, Belkhiri AB, Djerrou Z, Bahri L, Boulebda N, Pacha YH. Acute toxicity of Opuntia ficus indica and Pistacia lentiscus seed oils in mice . Afr J Tradit Complement Altern Med 2012; 9(4): 607-611.

[19] Han EH, Lim MK, Lee SH, Rahman MM, Lim YH. An oral toxicity test in rats and a genotoxicity study of extracts from the stems of Opuntia ficus-indica var. saboten . BMC Complement Altern Med 2019; 19: 31.

[20] Saad AB, Rjeibi I, Ncib S, Zouari N, Zourgui L. Ameliorative effect of cactus (Opuntia ficus indica) extract on lithium-induced nephrocardiotoxicity: A biochemical and histopathological study . BioMed Res Int 2017; 2017(1).

[21] Liaqat N, Jahan N, Rahman KU, Tahseen I, Anwar T, Qureshi H. Investigation of phytotherapeutic potential of herbal mixtures and their effects on salbutamol induced cardiotoxicity and hyperlipidemia in rabbits. Bot Stud 2023; 64(1): 23.

[22] Liu J, Zhou H, Song L, Yang Z, Qiu M, Wang J, et al. Anthocyanins: Promising natural products with diverse pharmacological activities. Molecules 2021; 26(13): 3807.

[23] Safaeian L, Zolfaghari B, Karimi S, Talebi A, Ghazvini MA. The effects of hydroalcoholic extract of Allium elburzense Wendelbo bulb on dexamethasone-induced dyslipidemia, hyperglycemia, and oxidative stress in rats . Res Pharm Sci 2018; 13(1): 22-29.

[24] Ghorbani L, Golkar P, Jafari R, Ahmadi M, Allafchian A. Phytochemicals, essential oils composition and antioxidant activity of Astragalus spp., Phlomis olivieri and Daphne mucronata in habitats of central Iran . Chem Biodivers 2023; 20(9). doi: 10.1002/cbdv.202300811.

[25] Safaeian L, Haghighatian Z, Zolfaghari B, Amindeldar M. Cardioprotective effects of Pinus eldarica bark extract on adrenaline-induced myocardial infarction in rats . Asian Pac J Trop Biomed 2023; 13(4): 148-155.

[26] Alimi H, Hfaiedh N, Bouoni Z, Sakly M, Rhouma KB. Evaluation of antioxidant and antiulcerogenic activities of Opuntia ficus indica f. inermis flowers extract in rats . Environ Toxicol Pharmacol 2011; 32(3): 406-416.

[27] Safaeian L, Mirian M, Bahrizadeh S. Evolocumab, a PCSK9 inhibitor, protects human endothelial cells against H₂O₂-induced oxidative stress . Arch Physiol Biochem 2022; 128(6): 1681-1686.

[28] Mesripour A, Karimi Z, Minaiyan M. Creatine and α-lipoic acid improved depressive behavior induced by interferon-α in mice: Malondialdehyde level remained unchanged. J Rep Pharm Sci 2021; 10(1): 124-129.

[29] Ben Saad A, Dalel B, Rjeibi I, Smida A, Ncib S, Zouari N, et al. Phytochemical, antioxidant and protective effect of cactus cladodes extract against lithium-induced liver injury in rats. Pharma Biol 2017; 55(1): 516-525.

[30] Tahri-Joutey M, Saih FE, El Kebbaj R, Gondcaille C, Vamecq J, Latruffe N, et al. Protective effect of Nopal cactus (Opuntia ficus-indica) seed oil against short-term lipopolysaccharides-induced inflammation and peroxisomal functions dysregulation in mouse brain and liver . Int J Mol Sci 2022; 23(19). doi: 10.3390/ijms231911849.

[31] Maiuolo J, Nucera S, Serra M, Caminiti R, Oppedisano F, Macrì R, et al. Cladodes of Opuntia ficus-indica (L.) Mill. possess important beneficial properties dependent on their different stages of maturity . Plants 2024; 13(10): 1365.

[32] Vogel B, Claessen BE, Arnold SV, Chan D, Cohen DJ, Giannitsis E, et al. ST-segment elevation myocardial infarction. Nat Rev Dis Primers 2019; 5(1): 1-20.

[33] Salama A, Mansour D, Hegazy R. The cardio and renoprotective role of ginseng against epinephrine-induced myocardial infarction in rats: Involvement of angiotensin Ⅱ type 1 receptor/protein kinase C. Toxicol Rep 2021; 8: 908-919.

[34] Bannon L, Merdler I, Bar N, Lupu L, Banai S, Jacob G, et al. The cardio-hepatic relation in STEMI. J Pers Med 2021; 11(12): 1241.

[35] Ndrepepa G. Aspartate aminotransferase and cardiovascular disease-a narrative review. J Lab Precis Med 2021; 6: 6.

[36] Grube B, Chong PW, Lau KZ, Orzechowski HD. A natural fiber complex reduces body weight in the overweight and obese: A double-blind, randomized, placebo-controlled study. Obesity 2013; 21(1): 58-64.

[37] Van Proeyen K, Ramaekers M, Pischel I, Hespel P. Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men . Int J Sport Nutr Exerc Metab 2012; 22(4): 284-291.

[38] Bakour M, Al-Waili N, El-Haskoury R, El-Menyiy N, Al-Waili T, Ali AL, et al. Comparison of hypotensive, diuretic and renal effects between cladodes of Opuntia ficus-indica and furosemide . Asian Pac J Trop Med 2017; 10(9): 900-906.

[39] Gouws CA, McKune A, Tee N, Somerset S, Mortazavi R. Prickly pear juice consumption after fat intake affects postprandial heart rate variability but not traditional risk factors of cardiovascular disease in healthy men. Nutrition 2022; 96. doi: 10.1016/j.nut.2021.111555.

[40] Giraldo-Silva L, Ferreira B, Rosa E, Dias AC. Opuntia ficus-indica fruit: A systematic review of its phytochemicals and pharmacological activities . Plants 2023; 12(3): 543.

[41] El-Hawary SS, Sobeh M, Badr WK, Abdelfattah MA, Ali ZY, El-Tantawy ME, et al. HPLC-PDA-MS/MS profiling of secondary metabolites from Opuntia ficus-indica cladode, peel and fruit pulp extracts and their antioxidant, neuroprotective effect in rats with aluminum chloride induced neurotoxicity . Saudi J Biol Sci 2020; 27: 2829-2838.

[42] Mansour R, Ben Ali H. Exploring chitosan as an ecofriendly agent to improve sustainable dyeing properties of cotton fabric dyed with (Opuntia Ficus-Indica L) fruit peel and its UV protection activity . Nat Fibers 2023; 20(1). doi: 10.1080/15440478.2022.2134263.

[43] Avila-Nava A, Calderón-Oliver M, Medina-Campos ON, Zou T, Gu L, Torres N, et al. Extract of cactus (Opuntia ficus indica) cladodes scavenges reactive oxygen species in vitro and enhances plasma antioxidant capacity in humans . J Funct Foods 2014; 10: 13-24.

[44] Li WQ, Li J, Liu WX, Wu LJ, Qin JY, Lin ZW, et al. Isorhamnetin: A novel natural product beneficial for cardiovascular disease. Curr Pharm Des 2022; 28(31): 2569-2582.

[45] Suchal K, Malik S, Gamad N, Malhotra RK, Goyal SN, Chaudhary U, et al. Kaempferol attenuates myocardial ischemic injury via inhibition of MAPK signaling pathway in experimental model of myocardial ischemia-reperfusion injury. Oxid Med Cell Longev 2016; 2016: 7580731.

[46] Guo Z, Liao Z, Huang L, Liu D, Yin D, He M. Kaempferol protects cardiomyocytes against anoxia/reoxygenation injury via mitochondrial pathway mediated by SIRT1. Eur J Pharmacol 2015; 761: 245-253.