Citrus peels have been reported useful in folk medicine for the management of cardiovascular diseases, but there is dearth of information on the possible mechanisms for their therapeutic action. The aim of this study was to investigate the effect of methanolic extracts from some citrus [lime (Citrus limon), tangerine (Citrus reticulata), shaddock (Citrus maxima)] peels on some enzymes relevant to the management of cardiovascular diseases [monoamine oxidase (MAO), phosphodiesterase-5 (PDE-5) and angiotensin-1-converting enzyme (ACE)].
Effect of methanolic extracts of lime, tangerine and shaddock peels on MAO, PDE-5 and ACE were carried out using standard methods. In addition, the ability of the extracts to prevent oxidative damage in rat heart homogenates was also investigated. Finally, the total polyphenol content of extracts was determined.
The results revealed that methanolic extracts of lime, tangerine and shaddock peels inhibited MAO, PDE-5, ACE and pro-oxidants induced lipid peroxidation in rat heart homogenate in a concentration-dependent manner.
Findings in this study revealed citrus peel methanolic extracts as natural inhibitor of enzymes (MAO, PDE-5 and ACE) implicated in cardiovascular diseases. Therefore, citrus peels could help in the management of cardiovascular diseases possibly through inhibition of these enzymes.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
 Ogihara T, Matsuzaki M, Matsuoka H, Shimamoto K, Shimada K, Rakugi H, et al. The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design. Hyper Res. 2005;28:331–8.10.1291/hypres.28.331Search in Google Scholar
 Hammoud RA, Vaccari CS, Nagamia SH, Khan BV. Regulation of the renin-angiotensin system in coronary atherosclerosis: a review of the literature. Vasc Health Risk Manag. 2007;3:937–45.Search in Google Scholar
 Balasuriya BWN, Rupasinghe HPV. Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Funct Foods Health Dis. 2011;5:172–88.10.31989/ffhd.v1i5.132Search in Google Scholar
 Balarini CM, Leal MA, Gomes IBS, Pereira TMC, Gava AL, Meyrelles SS, et al. Sildenafil restores endothelial function in the apolipoprotein E knockout mouse. J Transl Med. 2013;11:3.10.1186/1479-5876-11-3Search in Google Scholar
 Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol Ther. 2006;109:366–98.10.1016/j.pharmthera.2005.07.003Search in Google Scholar
 Di Lisa F, Kaludercic N, Carpi A, Menabo R, Giorgio M. Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p66 (Shc) and monoamine oxidase. Basic Res Cardiol. 2009;104:131–9.10.1007/s00395-009-0008-4Search in Google Scholar
 Amic D, Davidovic-Amic D, Beslo D, Trinajstic N. Structure-related scavenging activity relationship of flavonoids. Croatia Chem Acta. 2003;76:55–61.Search in Google Scholar
 Singleton VL, Orthofor R, Lamuela-Raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteau reagent. Methods Enzymol. 1999;299:152–78.10.1016/S0076-6879(99)99017-1Search in Google Scholar
 Meda A, Lamien CE, Romito M, Millogo J, Nacoulma OG. Determination of the total phenolic, flavonoid and proline contents in Burkina Faso honey, as well as their radical scavenging activity. Food Chem. 2005;91:571–7.10.1016/j.foodchem.2004.10.006Search in Google Scholar
 Cushman DW, Cheung HS. Spectrophotometric assay and properties of the angiotensin-1-converting enzyme of rabbit lung. Biochem Pharmacol. 1971;20:1637–48.10.1016/0006-2952(71)90292-9Search in Google Scholar
 Oboh G, Adebayo AA, Ademosun AO, Boligon AA. In-vitro inhibition of phosphodiesterase-5 and arginase activities in rat penile tissue by two Nigerian herbs (Hunteria umbellata and Anogeissus leiocarpus). J Basic Clin Physiol Pharmacol. 2017;28:393–401.10.1515/jbcpp-2016-0143Search in Google Scholar
 Nwanna EE, Adebayo AA, Oboh G, Ogunsuyi OB, Ademosun AO. Modulatory effects of alkaloid extract from Gongronema latifolium (utazi) and Lasianthera Africana (editan) on activities of enzymes relevant to neurodegeneration. J Dietary Supplements. 2018. DOI: 10.1080/19390211.2018.1426075Search in Google Scholar
 Shodehinde SA, Oyeleye SI, Olasehinde TA, Adebayo AA, Oboh G, Boligon AA. Lasianthera africana leaves inhibit α-amylase, α-glucosidase, angiotensin-1-converting enzyme activities and Fe2+-induced oxidative damage in pancreas and kidney homogenates. Orient Pharm Exp Med. 2017;17:41–9.10.1007/s13596-017-0256-zSearch in Google Scholar
 Zhang ZL, Lia QL, Lia BG, Zhangb Y, Gaob XP, Lia CQ. Three angiotensin converting enzyme inhibitors from Rabdosia coetsa. Phytomed. 2008;15:386–8.10.1016/j.phymed.2007.09.013Search in Google Scholar
 Umamaheswari M, Ajith MP, Asokkumar K. In vitro angiotensin converting enzyme inhibitory and antioxidant activities of seed extract of Apium graveolens Linn. Annals Biol Res. 2012;3:1274–82.Search in Google Scholar
 Je JY, Park PJ, Kim EK, Ahn CB. Antioxidant and angiotensin I converting enzyme inhibitory activity of Bambusae caulis in Liquamen. Food Chem. 2009;13:932–5.10.1016/j.foodchem.2008.08.022Search in Google Scholar
 Campos MRS, Guerrero LAC, Ancona DAB. Angiotensin-I converting enzyme inhibitory and antioxidant activities of peptide fractions extracted by ultrafiltration of cowpea Vigna unguiculata hydrolysates. J Sci Food Agric. 2010;90:2512–8.10.1002/jsfa.4114Search in Google Scholar PubMed
 Oboh G, Ademosun AO. Shaddock peels (Citrus maxima) phenolic extracts inhibit α-amylase, α-glucosidase and angiotensin-i-converting enzyme activities: a nutraceutical approach to diabetes management. Diab Met Synd Clin Res Rev. 2011;5:148–52.10.1016/j.dsx.2012.02.008Search in Google Scholar PubMed
 Pinto MD, Ranilla LG, Apostolidis E, Lajolo FM, Genovese MI, Shetty K. Evaluation of antihyperglycemia and antihypertension potential of native peruvian fruits using in vitro models. J Med Food. 2009;12:278–91.10.1089/jmf.2008.0113Search in Google Scholar PubMed
 Ademiluyi AO, Oboh G. In vitro anti-diabetes and antihypertension potential of phenolic extracts of selected underutilized tropical legumes. J Basic Clin Physiol Pharmacol. 2012;23:17–25.Search in Google Scholar
 Villeneuve C, Guilbeau-Frugier C, Sicard P, Lairez O, Ordener C, Duparc T, et al. p53-PGC-1alpha pathway mediates oxidative mitochondrial damage and cardiomyocyte necrosis induced by monoamine oxidase-A upregulation: role in chronic left ventricular dysfunction in mice. Antioxid Redox Signal. 2013;18:5–18.10.1089/ars.2011.4373Search in Google Scholar PubMed PubMed Central
 Oboh G, Adebayo AA, Ademosun AO. Phenolic-rich extracts of Eurycoma longifolia and Cylicodiscus gabunensis inhibit enzymes responsible for the development of erectile dysfunction and are antioxidants. J Basic Clin Physiol Pharmacol. 2018. DOI: 10.1515/jbcpp-2017-0160Search in Google Scholar PubMed
 Oboh G, Adebayo AA, Ademosun AO. Erection-stimulating, anti-diabetic and antioxidant properties of Hunteria umbellata and Cylicodiscus gabunensis water extractable phytochemicals. J Complement Integr Med. 2017. DOI: 10.1515/jcim-2016-0164Search in Google Scholar PubMed
 Abdelwahab SI, Mohamed AH, Mohamed OY, Oall M, Taha MME, Mohan S, et al. Erectogenic effects of Clerodendron capitatum: involvement of phosphodiesterase type-5 inhibition. Evidence- Based Compl Alt Med. 2012;Article ID 137386: 6.10.1155/2012/137386Search in Google Scholar PubMed PubMed Central
 Chan EC, Pannangpetch P, Woodman OL. Relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure-activity relationships. J Cardiovasc Pharmacol. 2000;35:326–33.10.1097/00005344-200002000-00023Search in Google Scholar PubMed
 Ko WC, Shih CM, Lai YH, Chen JH, Huang HL. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships. Biochem Pharmacol. 2004;68:2087–94.10.1016/j.bcp.2004.06.030Search in Google Scholar PubMed
 Ademosun AO, Oboh G, Passamonti S, Tramer F, Ziberna L, Boligon AA, et al. Inhibition of metalloproteinase and proteasome activities in colon cancer cells by citrus peel extracts. J Basic Clin Physiol Pharmacol. 2015;26:471–7.10.1515/jbcpp-2013-0127Search in Google Scholar PubMed
 Dell’ Agli M, Bush PA, Dorey FJ. Polyphenols in orange peels (citrus species) enhances relaxation corpus cavernosum tissue: implications to erectile physiology and dysfunction. Can J Pharmacol. 2006;73:1714–26.Search in Google Scholar
 Moon KH. Increased nitroxidative stress promotes mitochondrial dysfunction in alcoholic and nonalcoholic fatty liver diseases. Oxidative Med Cell Longevity. 2013;2013.10.1155/2013/781050Search in Google Scholar PubMed PubMed Central
 Kaisserlian CE, Razzouq N, Astier A, Paul M. Sodium nitroprusside stability at 1 μg/mL in aqueous solutions. Eur J Hosp PharmSci. 2005;11:88–90.Search in Google Scholar
 Calcerrada P, Peluffo G, Radi R. Nitric oxide-derived oxidants with a focus on peroxynitrite: molecular targets, cellular responses and therapeutic implications. Curr Pharm Des. 2011;17:3905–32.10.2174/138161211798357719Search in Google Scholar PubMed
 Wagner C, Fachinetto R, Dalla Corte CL, Brito VB, Severo D, Dias GDOC, et al. Quercitrin, a glycoside form of quercetin, prevents lipid peroxidation in vitro. Brain Res. 2006;1107:192–8.10.1016/j.brainres.2006.05.084Search in Google Scholar PubMed
© 2019 Walter de Gruyter GmbH, Berlin/Boston