Melatonin's Impact on Wound Healing

Abstract

Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin's effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin's potential roles in supporting effective wound healing.

Keywords: antioxidant; inflammation; injury; melatonin; oxidative stress; pineal gland; wound healing.

Figure 1

The chemical structure of melatonin. Melatonin structure is composed of an indole ring with an acetamide side chain (−CH₂CONH₂) and a methoxy side chain (−OCH₃) on a benzene ring.

Figure 2

Biosynthesis of melatonin and its degrading pathway. L-Tryptophan and serotonin are precursors of melatonin. Melatonin synthesis from L-tryptophan sequentially involves four enzyme-catalyzed reactions: hydroxylation, decarboxylation, acetylation, and methylation. The oxidation of melatonin can lead to the formation of various oxidized forms and metabolites. Melatonin undergoes secondary metabolism in the kidney and is excreted in the urine as an inactive metabolite 6-OHM. Abbreviations: AAD: aromatic amino acid decarboxylase; AANAT: Aralkylamine N-acetyltransferase; ASMT: Acetylserotonin O-methyltransferase; AFMK: N1-Acetyl-N2-formyl-5-methoxykynuramine; AMK: N1-Acetyl-5-methoxykynuramine; HIMOT: Hydroxy-O-methyltransferase; TPH1/2: Tryptophan Hydroxylase 1/2; NAT: N-Acetyltransferase; 5-HT: 5-hydroxytryptamine; 6-OHM: 6-Hydroxymelatonin; OH*: hydroxy radical.

Figure 3

Potential mechanisms of melatonin action in relation to local concentrations.

Figure 4

The roles of melatonin in antioxidant defense, anti-inflammatory response, and mitochondrial protection.

Figure 5

The roles of melatonin in vascular function, angiogenesis, neurological regulation, infection control, and oncostatic activity.

Figure 6

Melatonin for optimal support of wound healing. Beyond regulating circadian rhythm, melatonin exhibits (1) powerful antioxidant capacities, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, (6) anti-itch (anti-pruritic) effects, and (7) oncostatic effects.