Computational insights into the efficacy of chrysin as a caloric restriction mimetic.

Calorie restriction (CR) exerts its anti-aging beneficial effects by influencing key metabolic and stress-response regulators, including AMPK, SIRT1, COX-2, and catalase. A dietary flavonoid called Chrysin is thought to replicate some of the benefits of CR, although its multi-target molecular interactions are still unclear. This study employs molecular docking, MM-GBSA calculations, ADMET screening, and 100-ns molecular dynamics (MD) simulations to investigate the binding behavior, energy stability, and dynamic characteristics of Chrysin with respect to key CR-related proteins. According to docking studies, chrysin exhibits substantial affinity for all proteins examined, with AMPK showing the most favorable interaction profile. Catalase exhibited comparatively decreased binding but retained its structural integrity, while SIRT1 and COX-2 showed moderate affinity. MD simulations revealed that the COX-2 complex exhibited significant instability, while catalase provided modest stabilization, and AMPK and SIRT1 formed extremely stable complexes. The key catalytic domains of these proteins are not disrupted by chrysin binding, according to RMSF analysis. High oral absorption capacity and good drug-likeness were predicted by ADMET. All things considered, chrysin seems to function as a promising calorie-restriction mimetic by interacting with several metabolic regulators, with strong and consistent interactions seen between AMPK and SIRT1. These findings support the potential for additional research as a multi-target therapeutic anti-aging alternative.