Geraniol Attenuates Cerebral Ischemia-Reperfusion Injury by Suppressing PINK1/Parkin Mediated Mitophagy

Abstract

Introduction

Cerebral ischemia-reperfusion injury (CIRI) leads to brain damage and arises when blood flow to the brain is initially restricted and subsequently restored. Geraniol, a monoterpenoid alcohol presented in essential oil, showed multiple pharmacological activities including antimicrobial, anticancer but its neuroprotection in CIRI via PINK1/parkin mitophagy has not been explored. So this study aim to determine the therapeutic potential of geraniol in CIRI, particularly focus on its ability to suppress PINK1/Parkin-mediated mitophagy.

Methods

The experiment was carried out in PC12 cell line, sourced from American Type Culture Collection (ATCC). The cells were cultured, Oxygen–glucose deprivation/reoxygenation (OGD/R) model was prepared and underwent geraniol treatment. The cell viability assay (at different concentration of geraniol and different reoxygenation time) was performed. Protein expression was analyzed by western blotting, adenosine triphosphate (ATP) content was measured to assess mitochondrial function and apoptosis was determined.

Results

The result of cell viability assay showed that 20 µM geraniol did not significantly affect cell viability compared with the control and cell viability increased with reoxygenation time in both OGD/R as well as OGD/R group treated with geraniol. Western blot result showed that, compared with the control group, OGD/R increased PINK1, Parkin, Beclin1, and LC3B levels, while decreasing TOMM20 and P62. Treatment with 20 µM geraniol reversed these changes, by reducing PINK1, Parkin, Beclin1, and LC3B expression and restoring TOMM20 and P62 levels. Similarly geraniol treatment increased viable cell and decreased apoptosis cell compared to OGD/R model.

Conclusion

Geraniol was found to reduce OGD induced injury by suppressing PINK1/Parkin mitophagy.