Phenolic acids: mechanisms of circadian clock-sleep regulation and metabolic modulation

The circadian clock and sleep are tightly linked in mammals; they regulate central and peripheral oscillators and react dynamically to sleep deprivation and circadian misalignment, affecting metabolic health. Genetic evidence highlights the impact of single-gene variants, such as <i>Per2, Cry1</i>, and <i>Dec2</i>, on a person’s sleep. On a related note, clinical studies have confirmed that chronic circadian disruption plays a role in disorders like insomnia, obstructive sleep apnea, and metabolic syndrome. Importantly, phenolic acids, bioactive compounds found in cereals, fruits, and coffee, are shown by growing research to influence the circadian clock and sleep. They can modulate this through antioxidant, anti-inflammatory, and neurotransmitter-related pathways. Chlorogenic, rosmarinic, caffeic, ferulic, cichoric, salicylic, and gallic acids demonstrate differential capacities to regulate core clock gene expression, melatonin metabolism, neurotransmission, and peripheral metabolic rhythms. These interactions provide mechanistic insights into how phenolic acids may ameliorate sleep disturbances, restore circadian alignment, and improve metabolic resilience. The phenolic acids discussed in this review as promising candidates for precision strategies targeting sleep and circadian rhythm-related disorders.