Oleanolic acid : a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction

dc.contributor.authorMapanga, Rudo F.en_ZA
dc.contributor.authorRajamani, Uthraen_ZA
dc.contributor.authorDlamini, Nonkululekoen_ZA
dc.contributor.authorZungu-Edmondson, Makhosazaneen_ZA
dc.contributor.authorKelly-Laubscher, Roisonen_ZA
dc.contributor.authorShafiullah, Mohammeden_ZA
dc.contributor.authorWahab, Athiqen_ZA
dc.contributor.authorHasan, Mohamed Y.en_ZA
dc.contributor.authorFahim, Mohamed A.en_ZA
dc.contributor.authorRondeau, Phillipeen_ZA
dc.contributor.authorBourdon, Emmanuelen_ZA
dc.contributor.authorEssop, M. Faadielen_ZA
dc.identifier.citationMapanga, R. F., et al. 2012. Oleanolic acid : a novel cardioprotective agent that blunts hperglycemia-induced contractile dysfunction. PLoS ONE, 7(10): 1-17, doi: 10.1371/journal.pone.0047322en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.issn1932-6203 (print)
dc.identifier.otherdoi: 10.1371/journal.pone.0047322
dc.descriptionCITATION: Mapanga, R. F., et al. 2012. Oleanolic acid : a novel cardioprotective agent that blunts hperglycemia-induced contractile dysfunction. PLoS ONE, 7(10): 1-17, doi: 10.1371/journal.pone.0047322.en_ZA
dc.descriptionThe original publication is available at
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund.en_ZA
dc.description.abstractDiabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP) and a dysfunctional ubiquitin-proteasome system (UPS) as potential mediators of this process. Since oleanolic acid (OA; a clove extract) possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS) and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1) H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose); and subsequently treated with two OA doses (20 and 50 mM) for 6 and 24 hr, respectively; 2) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose) for 60 min, followed by 20 min global ischemia and 60 min reperfusion 6 OA treatment; 3) In vivo coronary ligations were performed on streptozotocin treated rats 6 OA administration during reperfusion; and 4) Effects of long-term OA treatment (2 weeks) on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These findings are promising since it may eventually result in novel therapeutic interventions to treat acute hyperglycemia (in non-diabetic patients) and diabetic patients with associatedcardiovascular complications.en_ZA
dc.description.sponsorshipThis work was supported by the South African National Research Foundation and Stellenbosch University (to MFE). Experimental work conducted at Universite´ de La Re´union was supported by the Ministe`re de l’Enseignement Supe´ rieur et de la Recherche and the Universite´ de La Re´union and the Conseil Re´gional de La Re´union and l’Europe (to EB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_ZA
dc.format.extent17 pages : illustrationsen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.subjectOleanolic Acid therapyen_ZA
dc.subjectContractile dysfunctionen_ZA
dc.subjectHyperglycemia -- Treatmenten_ZA
dc.subjectCardioprotective agentsen_ZA
dc.titleOleanolic acid : a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunctionen_ZA
dc.description.versionPublisher's versionen_ZA
dc.rights.holderAuthors retain copyrighten_ZA

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