What does this research mean for the field?

The natural monoterpenoid geraniol enhances in vivo antioxidant defense and resistance to oxidative stress in C. elegans, an effect that is strictly dependent on the activation of the SKN-1/Nrf2 transcription factor. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To investigate how geraniol enhances antioxidant defense and resilience to oxidative stress in Caenorhabditis elegans.

April 23, 2026Natural Products and Bioprospecting0 citationsOpen Access

Natural monoterpenoid geraniol promotes antioxidant defense and stress tolerance via SKN-1/Nrf2 activation in Caenorhabditis elegans

SRStefano Romussi ALAilin Lacour DRDiego Rayes

Key Points

To investigate how geraniol enhances antioxidant defense and resilience to oxidative stress in Caenorhabditis elegans.
Utilized Caenorhabditis elegans to assess the effects of geraniol in vivo.
Employed GFP-reporter strains to characterize molecular mechanisms.
Conducted genetic epistasis analysis using mutant strains to identify essential pathways.
Geraniol significantly reduces intracellular reactive oxygen species levels.
It enhances resistance to acute oxidative stress induced by juglone.
SKN-1 is essential for geraniol's protective effects against oxidative stress.

Abstract

Abstract Oxidative stress (OS) is a major contributor to aging and the pathogenesis of numerous conditions, including diabetes, neurodegenerative, cardiovascular, and autoimmune disorders. Consequently, therapeutic strategies aimed at enhancing endogenous cytoprotective pathways have gained significant interest. Plant-derived essential oils represent attractive sources for such interventions due to their natural origin and low toxicity; specifically, the monoterpenoid geraniol, a principal component of rose oil, has demonstrated promising antioxidant properties in vitro. In this study, we utilized Caenorhabditis elegans to investigate the in vivo efficacy and molecular mechanisms of geraniol effect. Our results show that geraniol significantly reduces intracellular reactive oxygen species and enhances resistance to acute OS induced by juglone. Mechanistic characterization using GFP-reporter strains revealed that geraniol activates the DAF-16/FOXO and SKN-1/Nrf2 transcription factors, while surprisingly causing a slight but consistent downregulation of the HSF-1-mediated heat-shock response. Crucially, genetic epistasis analysis using null/hypomorphic mutants demonstrated that only SKN-1 is strictly essential for geraniol-mediated protection against induced OS. In conclusion, this study underscores the utility of C. elegans as a robust and accessible platform for the pharmacological screening of natural products. Our findings establish geraniol, a key constituent of rose oil, as a multifunctional modulator of cellular defenses that orchestrates multiple cytoprotective pathways, identifying the SKN-1-dependent response as a critical driver of its antioxidant efficacy in C. elegans . By delineating this specific genetic requirement, these results provide a mechanistic foundation that supports the therapeutic potential of geraniol in mitigating aging and pathophysiology driven by OS. Graphical abstract

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