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

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...

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Vydáno v:Neurochemical research Ročník 46; číslo 8; s. 2131 - 2142
Hlavní autoři: Mnafgui, Kais, Ghazouani, Lakhdar, Hajji, Raouf, Tlili, Abir, Derbali, Fatma, da Silva, Francisco Ivan, Araújo, Joabe Lima, de Oliveira Schinoff, Bianca, Bachega, José Fernando Ruggiero, da Silva Santos, Antônia Laíres, Allouche, Noureddine
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Springer US 01.08.2021
Springer Nature B.V
Témata:
Acetylcholinesterase - metabolism
Angiotensin
Animal models
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Brain
Brain - pathology
Brain damage
Brain Edema - pathology
Brain Edema - prevention & control
Brain injury
Catalase
Cell Biology
Clopidogrel
Clopidogrel - therapeutic use
Creatine
Creatine kinase
Edema
Fibrinogen
Free Radical Scavengers - metabolism
Free Radical Scavengers - therapeutic use
Glutathione
Glutathione peroxidase
Humans
Hyponatremia
Hyponatremia - prevention & control
Infarction, Middle Cerebral Artery - drug therapy
Infarction, Middle Cerebral Artery - pathology
Iridoid Glucosides - metabolism
Iridoid Glucosides - therapeutic use
Ischemia
Kinases
Lactic acid
Male
Molecular docking
Molecular Docking Simulation
Neurochemistry
Neurology
Neuroprotection
Neuroprotective Agents - metabolism
Neuroprotective Agents - therapeutic use
Neurosciences
Oleuropein
Original Paper
Oxidative stress
Oxidative Stress - drug effects
Peptidyl-dipeptidase A
Peptidyl-Dipeptidase A - metabolism
Peroxidase
Protein Binding
Protein disulfide-isomerase
Protein Disulfide-Isomerases - metabolism
Rats
Rats, Wistar
Rodents
Stroke
Superoxide dismutase
Thiobarbituric acid
Thiobarbituric Acid Reactive Substances - metabolism
Tissue analysis
Transforming growth factor-b1
Protein disulfide isomerase
Oxidative stress
Stroke
ACE
Oleuropein
ISSN:0364-3190, 1573-6903, 1573-6903
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0364-3190
1573-6903
1573-6903
DOI:10.1007/s11064-021-03351-9