Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Complementary and Integrative Medicine

Editor-in-Chief: Lui, Edmund

Ed. by Ko, Robert / Leung, Kelvin Sze-Yin / Saunders, Paul / Suntres, PH. D., Zacharias

CiteScore 2017: 1.41

SCImago Journal Rank (SJR) 2017: 0.472
Source Normalized Impact per Paper (SNIP) 2017: 0.564

See all formats and pricing
More options …

Modulatory effect of some citrus (Citrus limon, Citrus reticulata, Citrus maxima) peels on monoamine oxidase, phosphodiesterase-5 and angiotensin-1 converting enzyme activities in rat heart homogenate

Ayokunle O. Ademosun
  • Department of Biochemistry, Functional Foods and Nutraceutical Unit, Federal University of Technology, P.M.B. 704, Akure 340001, Nigeria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Adeniyi A. Adebayo
  • Department of Biochemistry, Functional Foods and Nutraceutical Unit, Federal University of Technology, P.M.B. 704, Akure 340001, Nigeria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ganiyu Oboh
  • Corresponding author
  • Department of Biochemistry, Functional Foods and Nutraceutical Unit, Federal University of Technology, P.M.B. 704, Akure 340001, Nigeria
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-08-11 | DOI: https://doi.org/10.1515/jcim-2018-0067



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.

Keywords: angiotensin-1-converting enzyme; citrus peels; lipid peroxidation; monoamine oxidase


  • [1]

    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.CrossrefGoogle Scholar

  • [2]

    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.PubMedGoogle Scholar

  • [3]

    Balasuriya BWN, Rupasinghe HPV. Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Funct Foods Health Dis. 2011;5:172–88.Google Scholar

  • [4]

    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.Web of ScienceCrossrefPubMedGoogle Scholar

  • [5]

    Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol Ther. 2006;109:366–98.PubMedCrossrefGoogle Scholar

  • [6]

    Takimoto E, Kass DA. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension. 2007;49:241–8.CrossrefWeb of SciencePubMedGoogle Scholar

  • [7]

    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.Web of ScienceCrossrefPubMedGoogle Scholar

  • [8]

    Belitz HD, Grosch W. Fruits and fruit products. In: Hadziyev D, editor. Food chemistry. Berlin, Heidelberg: Springer Verlag, 1999:748–99.Google Scholar

  • [9]

    Amic D, Davidovic-Amic D, Beslo D, Trinajstic N. Structure-related scavenging activity relationship of flavonoids. Croatia Chem Acta. 2003;76:55–61.Google Scholar

  • [10]

    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.CrossrefGoogle Scholar

  • [11]

    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.CrossrefGoogle Scholar

  • [12]

    Cushman DW, Cheung HS. Spectrophotometric assay and properties of the angiotensin-1-converting enzyme of rabbit lung. Biochem Pharmacol. 1971;20:1637–48.CrossrefGoogle Scholar

  • [13]

    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.PubMedGoogle Scholar

  • [14]

    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: CrossrefGoogle Scholar

  • [15]

    Turski W, Turska E, Grossbel M. Modification of spectrophotometric method of determination of monoamine-oxidase. Enzyme. 1973;14:211–20.Google Scholar

  • [16]

    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.CrossrefGoogle Scholar

  • [17]

    Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Annals Biochem. 1979;95:351–8.CrossrefGoogle Scholar

  • [18]

    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.CrossrefGoogle Scholar

  • [19]

    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.Google Scholar

  • [20]

    Coates D. The angiotensin converting enzyme (ACE). Int J Biochem Cell Biol. 2003;35:769–73.PubMedCrossrefGoogle Scholar

  • [21]

    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.Web of ScienceGoogle Scholar

  • [22]

    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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [23]

    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.Google Scholar

  • [24]

    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.Web of ScienceCrossrefPubMedGoogle Scholar

  • [25]

    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.Google Scholar

  • [26]

    Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417:1–13.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [27]

    Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335–44.PubMedCrossrefGoogle Scholar

  • [28]

    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.CrossrefPubMedGoogle Scholar

  • [29]

    Youdim MB, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci. 2006;7:295–309.PubMedCrossrefGoogle Scholar

  • [30]

    Lue TF. Erectile dysfunction. N Engl J Med. 2000;342:1802–13.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [31]

    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: CrossrefPubMedGoogle Scholar

  • [32]

    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: CrossrefPubMedGoogle Scholar

  • [33]

    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.Web of ScienceGoogle Scholar

  • [34]

    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.CrossrefPubMedGoogle Scholar

  • [35]

    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.PubMedCrossrefGoogle Scholar

  • [36]

    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.PubMedGoogle Scholar

  • [37]

    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.Google Scholar

  • [38]

    Moon KH. Increased nitroxidative stress promotes mitochondrial dysfunction in alcoholic and nonalcoholic fatty liver diseases. Oxidative Med Cell Longevity. 2013;2013.Google Scholar

  • [39]

    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.Google Scholar

  • [40]

    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.CrossrefPubMedGoogle Scholar

  • [41]

    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.CrossrefPubMedGoogle Scholar

  • [42]

    Chu Y, Sun J, Wu X, Liu RH. Antioxidant and antiproliferative activity of common vegetables. J Agric Food Chem. 2002;50:6910–6.PubMedCrossrefGoogle Scholar

About the article

Received: 2018-05-22

Accepted: 2018-06-25

Published Online: 2018-08-11

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.

Citation Information: Journal of Complementary and Integrative Medicine, Volume 16, Issue 1, 20180067, ISSN (Online) 1553-3840, DOI: https://doi.org/10.1515/jcim-2018-0067.

Export Citation

© 2019 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in