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Review
. 2025 Aug:82:102123.
doi: 10.1016/j.smrv.2025.102123. Epub 2025 Jun 26.

Melatonin: beyond circadian regulation - exploring its diverse physiological roles and therapeutic potential

Affiliations
Review

Melatonin: beyond circadian regulation - exploring its diverse physiological roles and therapeutic potential

Min Jia et al. Sleep Med Rev. 2025 Aug.

Abstract

As an indoleamine with a long evolutionary history, melatonin's physiological functions have evolved from its initial role in regulating skin pigmentation in fish and amphibians to encompass a broad spectrum of critical physiological regulatory functions. In mammals, melatonin primarily serves to regulate the circadian rhythm system, which is essential for maintaining the sleep-wake cycle. Abnormal melatonin secretion has been strongly associated with the development of sleep disorders, which are recognized as significant risk factors for various chronic diseases. This article aims to comprehensively examine the diverse physiological functions of melatonin beyond its role in regulating circadian rhythms and the sleep-wake cycle, while analyzing its mechanisms of action in modulating oxidative stress, anti-inflammatory responses, and mitochondrial function. Furthermore, this article evaluates the multifaceted effects of melatonin on energy metabolism, bone metabolism, nervous system regulation, and cardiovascular health at pharmacological doses, highlighting its importance in managing sleep disorders. By synthesizing current research findings, this article provides an objective assessment of the scientific foundation for melatonin's role in enhancing sleep quality and promoting overall health, while emphasizing the need to distinguish between its physiological and pharmacological effects.

Keywords: Circadian rhythm; Health supplement; Insomnia; Melatonin; Mitochondria.

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Conflict of interest statement

Declaration of competing interest All authors do not have any possible conflicts of interest for this manuscript.

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