Oleuropein Modulates Mitophagy and Metabolism in Cardiomyocyte Via the PINK1/Parkin Signaling Pathway

Sep 26, 2025Drug development research

Oleuropein may influence heart muscle cell energy use and cleanup through the PINK1/Parkin pathway

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Abstract

OLEU (up to 200 μM) dose-dependently restored cell viability and reduced oxidative stress in cardiomyocytes.

OLEU alleviated oxidative stress by reducing reactive oxygen species (ROS) and normalizing antioxidant enzyme levels.
Mitochondrial health was supported as OLEU mitigated mitochondrial membrane potential collapse and ATP depletion.
OLEU enhanced the expression of PINK1 and Parkin, promoting the removal of damaged mitochondria through a process known as mitophagy.
In rats with induced myocardial infarction, OLEU preserved myocardial structure and improved cardiac function.
Metabolomic analysis indicated that OLEU modulated pathways related to arginine/proline and lipids.

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‌Oleuropein (OLEU), a natural polyphenol, exhibits cardioprotective potential through mitochondrial modulation, yet its precise mechanisms remain elusive. This study elucidates OLEU's role in alleviating oxidative stress and regulating mitochondrial quality control via the PINK1/Parkin pathway. In vitro, H9C2 cardiomyocytes exposed to H₂O₂-induced oxidative stress were treated with OLEU (0-200 μM), and analyses included cell viability, ROS, SOD, MDA, ΔΨm, ATP, PINK1/Parkin expression and detection of Mitophagic Flux. In vivo, myocardial infarction (MI) was induced in SD rats via coronary ligation, followed by OLEU administration, with assessments of cardiac function, histopathology, and mitophagy using echocardiography, electron microscopy, immunohistochemistry and immunofluorescence. Results showed that OLEU (≤200 μM) dose-dependently restored cell viability, reduced ROS, and normalized SOD/MDA (p < 0.05), while mitigating ΔΨm collapse and ATP depletion, indicating enhanced mitochondrial bioenergetics. OLEU upregulated PINK1/Parkin, promoting mitophagic clearance of damaged mitochondria, and metabolomic analysis revealed modulation of arginine/proline and lipid pathways. In MI rats, OLEU attenuated ROS, preserved myocardial structure, and improved cardiac function, supported by elevated mitophagy in electron microscopy. These findings demonstrate that OLEU protects cardiomyocytes by suppressing oxidative stress, stabilizing mitochondrial integrity, and activating PINK1/Parkin-mediated mitophagy, highlighting its therapeutic potential for myocardial injury and mitochondrial dysfunction.

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Oleuropein Modulates Mitophagy and Metabolism in Cardiomyocyte Via the PINK1/Parkin Signaling Pathway

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