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Oleuropein Protects Against Cerebral Ischemia Injury in Rats: Molecular Docking, Biochemical and Histological Findings

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Abstract

This study was designed to evaluate the underlying protective mechanisms of oleuropein involved in alleviating brain damage in a rat model of ischemic stroke. Male Wistar rats were divided into four groups; Control, stroke (MCAO), MCAO + clopidogrel (Clop) and MCAO + oleuropein (Ole). Results showed that the MCAO group evidenced significant brain edema (+ 9%) as well as increases of plasma cardiac markers such as lactate deshydrogenase (LDH), creatine kinase (CK-MB), fibrinogen and Trop-T by 11 %, 43%, 168 and 590%, respectively, as compared to the control group. Moreover, infarcted rats exhibited remarkable elevated levels of angiotensin converting enzyme (ACE), both in plasma and brain tissue, with astrocyte swelling and necrotic neurons in the infarct zone, hyponatremia, and increased rate of thiobarbituric acid-reactive substances (TBARS) by 89% associated with decreases in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) by 51%, 44 and 42%, respectively, compared to normal control rats. However, MCAO rats treated with oleuropein underwent mitigation of cerebral edema, correction of hyponatremia, remarkable decrease of plasma fibrinogen and cardiac dysfunctional enzymes, inhibition of ACE activity and improvement of oxidative stress status in brain tissue. Furthermore, in silico analysis showed considerable inhibitions of ACE, protein disulfide isomerase (PDI) and TGF-β1, an indicative of potent anti-embolic properties. Overall, oleuropein offers a neuroprotective effect against ischemic stroke through its antioxidative and antithrombotic activities.

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Acknowledgements

This research was supported by the Tunisian Ministry of Higher Education and Scientific Research and the Tunisian Ministry of Public Health.

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Authors and Affiliations

  1. Laboratory of Animal Physiology, Faculty of Sciences of Sfax, University of Sfax, P.O. Box 95, 3052, Sfax, Tunisia

    Kais Mnafgui

  2. Research Unit of Macromolecular Biochemistry and Genetics, Faculty of Sciences of Gafsa, University of Gafsa, 2112, Gafsa, Tunisia

    Lakhdar Ghazouani

  3. Service de Médecine Interne, Faculté de Médecine de Sousse, Hôpital de Sidi Bouzid, Université de Sousse, Sidi Bouzid 9100, 4200, Sousse, Tunisia

    Raouf Hajji & Fatma Derbali

  4. Faculty of Medicine of Monastir, 5000, Monastir, Tunisia

    Abir Tlili

  5. Department of Chemistry, Center for Natural Sciences, Federal University of Piauí, Campus Ministro Petrônio Portela, 64049-550, Teresina, PI, Brazil

    Francisco Ivan da Silva & Antônia Laíres da Silva Santos

  6. Programa de Pós-Graduação em Nanociência e Nanobiotecnologia, Departamento de Genética e Morfologia, Universidade de Brasília, s/n Campus Universitário Darcy Ribeiro, 70910-900, Brasília, DF, Brasil

    Joabe Lima Araújo

  7. Departamento de Farmacociências, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

    Bianca de Oliveira Schinoff & José Fernando Ruggiero Bachega

  8. Programa de pós-graduação em Biologia Celular e molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    José Fernando Ruggiero Bachega

  9. Laboratory of Organic Chemistry LR17ES08 (Natural Substances Team), Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia

    Noureddine Allouche

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  1. Kais Mnafgui
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Mnafgui, K., Ghazouani, L., Hajji, R. et al. Oleuropein Protects Against Cerebral Ischemia Injury in Rats: Molecular Docking, Biochemical and Histological Findings. Neurochem Res 46, 2131–2142 (2021). https://doi.org/10.1007/s11064-021-03351-9

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