Abstract

Oxidative stress is a fundamental challenge to cellular integrity, contributing significantly to aging and various pathologies. This study investigates the protective efficacy of two natural compounds, **Mangiferin** and **trans-Cinnamic Acid**, against induced oxidative stress using the model organism *Caenorhabditis elegans*. The research objective was to determine if these compounds could mitigate cellular damage and extend lifespan, particularly in strains with compromised metabolic signaling. We utilized both wild-type (N2) worms and a loss-of-function mutant for the **aak-2** gene, which encodes the catalytic subunit of AMP-activated protein kinase (AMPK). AMPK is a critical sensor of cellular energy status and a key regulator of stress response pathways, often influencing mitochondrial function and membrane stability. Methods involved pre-treating worms with the compounds and subsequently exposing them to an oxidative stressor (e.g., paraquat or hydrogen peroxide), followed by assays for survival, reactive oxygen species (ROS) levels, and lipid peroxidation, a marker of membrane damage. Our findings indicate that both Mangiferin and trans-Cinnamic Acid significantly enhanced stress resistance and reduced intracellular ROS accumulation in the wild-type strain. Crucially, the protective effects were partially or fully attenuated in the *aak-2* mutant, suggesting that the mechanism of action is, at least in part, dependent on the conserved AMPK signaling pathway. These results highlight the potential of these phytochemicals as therapeutic agents to bolster cellular defenses against oxidative damage and provide new insights into the interplay between natural compounds, metabolic signaling, and cellular stress resilience.