Citronellal Alleviates Myocardial Senescence by Enhancing Mitochondrial Autophagy via AMPKα–PINK1/Parkin Pathway

Feb 1, 2026Phytotherapy research : PTR

Citronellal May Reduce Heart Aging by Boosting Mitochondrial Cleanup Through the AMPKα-PINK1/Parkin Pathway

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Citronellal (CT) at 200 mg/kg significantly reduces myocardial oxidative stress and alleviates cardiomyocyte senescence.

CT treatment mitigates the senescent characteristics of cardiomyocytes in both mouse and cell models.
The reduction in oxidative stress levels is observed following CT administration.
CT enhances the process of mitophagy by activating the AMPKα-mediated PINK1/Parkin pathway.
Bioinformatics analyses suggest that oxidative stress resistance and mitophagy regulation are key mechanisms of CT's cardioprotective effects.
These findings indicate CT's potential as a cardioprotective agent in addressing cardiac aging and associated conditions.

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Cardiomyocyte senescence contributes to the progression of multiple cardiac diseases, with oxidative stress identified as a central pathophysiological mechanism. Previous animal experiments demonstrated that citronellal (CT), administered at 200 mg/kg in rats, exerted significant cardioprotective effects. However, the molecular mechanisms underlying these effects remain unclear. This study aimed to investigate the role of CT in mitigating myocardial senescence and to elucidate its mechanistic pathways. Doxorubicin-induced myocardial senescence mouse models and H9C2 cardiomyocyte senescence models were established. SA-β-gal staining, Western blotting, immunofluorescence, and immunohistochemistry were employed to evaluate senescence and oxidative stress markers. Network pharmacology analysis and molecular docking were conducted to predict CT targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify potential mechanisms of action. CT treatment significantly reduced myocardial oxidative stress levels, ameliorated senescent phenotypes in both in vivo and in vitro models, and enhanced mitophagy by activating the AMPKα-mediated PINK1/Parkin pathway. Bioinformatics analyses further supported the involvement of oxidative stress resistance and mitophagy regulation as central mechanisms underlying CT's cardioprotective effects. Citronellal effectively alleviates cardiomyocyte senescence by reducing oxidative stress and promoting mitophagy through activation of the AMPKα-PINK1/Parkin signaling pathway. These findings provide experimental evidence supporting CT as a promising cardioprotective agent and highlight a novel mechanism of action that may inform future therapeutic strategies for cardiac aging and related diseases.

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Citronellal Alleviates Myocardial Senescence by Enhancing Mitochondrial Autophagy via AMPKα–PINK1/Parkin Pathway

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