Targeting cortisol dysregulation through bioactive compounds: implications for stress, sleep, and mental wellness
Abstract
Stress and sleep disturbances have emerged as significant global health challenges, intricately linked through the hypothalamic–pituitary–adrenal (HPA) axis. Cortisol, the primary stress hormone, serves as a key biomarker of HPA axis activity, influencing metabolism, immune response, and sleep regulation. Chronic elevation of cortisol disrupts circadian rhythm, inhibits melatonin synthesis, and contributes to insomnia, anxiety, and fatigue. Therefore, identifying bioactive compounds capable of modulating cortisol and restoring HPA axis balance offers a natural strategy for improving stress resilience and sleep quality. This review consolidates scientific evidence on several plant-derived and microbial bioactive compounds with cortisol-lowering and sleep-promoting effects. Bioactive compounds that modulate the HPA axis, therefore, represent a multidimensional therapeutic opportunity, acting not only on endocrine regulation but also on neurochemical balance and immune modulation. Integrating these compounds into dietary or nutraceutical interventions could provide a preventive and restorative approach for individuals experiencing chronic stress or sleep disorders. Withania somnifera (ashwagandha) exhibits adaptogenic properties via withanolides that downregulate cortisol and improve sleep onset. Panax ginseng contains ginsenosides that modulate stress hormone release and enhance neural adaptability. Ganoderma lucidum (reishi mushroom) triterpenoids exert anxiolytic and…
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