Pandi-Perumal · The FEBS journal 2006 · narrative review · n=?

Melatonin: Nature's most versatile biological signal?

Cited 872 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of biological mechanisms and clinical applications without systematic methodology.

PubMed 16817850 · doi:10.1111/j.1742-4658.2006.05322.x · record verified 2026-08-31

What was done

This narrative review summarizes published literature on the evolutionary distribution, tissue synthesis, physiological signaling pathways, and therapeutic implications of melatonin across organisms ranging from unicellular species and plants to vertebrates, including humans.

What was found

The abstract reports no primary quantitative data or effect sizes. It describes melatonin as a nocturnal hormone synthesized primarily by pinealocytes under suprachiasmatic nucleus regulation, as well as in extrapineal sites including the retina, gastrointestinal tract, skin, bone marrow, and lymphocytes. Reported physiological functions include free radical scavenging, up-regulation of antioxidant enzymes, antiapoptotic signaling during ischemia, immune enhancement, and circadian timekeeping. Clinically, melatonin is described as facilitating sleep in circadian rhythm disorders (jet lag, shift-work disorder) and insomnia in elderly or depressed populations, while the analog agomelatine is noted as effective for major depressive and bipolar affective disorders.

Why it matters

The review synthesizes evidence framing melatonin not merely as a pineal hormone, but as an evolutionarily ubiquitous cytoprotective and chronological signaling molecule with clinical relevance across sleep medicine and psychiatry.

Limits

The abstract provides a broad narrative summary without systematic search criteria, meta-analytic pooling, or risk-of-bias evaluation. No quantitative effect sizes or sample sizes are reported, and melatonin's photoperiodic regulatory influence in humans is noted to remain under investigation.

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