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Melatonin: New Places in Therapy

  • ORIGINAL PAPER
  • Published:
Bioscience Reports

Abstract

The fact that the full extent of the function of the pineal gland has not yet been elucidated, has stimulated melatonin research worldwide. This review introduces melatonin’s mechanism of action, direct and indirect antioxidant actions as well as the antioxidant properties of its metabolites, 6-hydroxymelatonin (6-OHM) and N-acetyl-N-formyl-5-methoxykynurenamine (AFMK). At present the mechanism of action is proposed to be receptor-, protein- and nonprotein-mediated. From its popular role in the treatment of jetlag, melatonin is now implicated in the reduction of oxidative stess, both as a free radical scavenger and antioxidant. Melatonin’s direct scavenging action in respect of the following will be discussed: superoxide anions, hydrogen peroxide, hydroxyl radicals, singlet oxygen, peroxy radicals and nitric oxide/peroxy nitrite anions. In addition melatonin also possesses indirect antioxidant activity and the role of its metabolites, AFMK and 6-OHM will be presented. It is these free radical scavenging and antioxidant properties of melatonin that has shifted the focus from that of merely strengthening circadian rhythms to that of neuroprotectant: a new place in therapy.

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Abbreviations

6-OHM:

6-hydroxymelatonin

AFMK:

N-acetyl-N-formyl-5-methoxykynurenamine

GPx:

Glutathione peroxidase

GRd:

Glutathione reductase

SOD:

Superoxide dismutase

NOS:

Nitic oxide synthase

CaCaM:

Ca2+-calmodulin

NO• :

Nitric oxide

iNOS:

inducible Nitric oxide synthetase

•OH:

Hydroxyl radical

\( {\text{O}}^{{ - \bullet }}_{{\text{2}}} \) :

Superoxide anions

H2O2 :

Hydrogen peroxide

CAT:

Catalase

THA:

Terephthalic acid

DHBA:

Dihydroxybenzoic acid

1O2:

Singlet oxygen

LOO• :

Peroxyl radicals

ONOO− :

Nitric oxide/peroxynitrite anions

G6PD:

Glucose-6-phosphate dehydrogenase

GSH:

Reduced glutathione

AD:

Alzheimers disease

PD:

Parkinsons disease

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Acknowledgements

The authors thank NRF for funding. DSM thanks the MRC for the postdoctoral fellowship. The authors would also like to thank Rhodes University in Grahamstown, South Africa and James Cook University in Townsville, Australia for financial assistance.

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Authors and Affiliations

  1. Faculty of Pharmacy, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa

    Deepa S. Maharaj & Santy Daya

  2. School of Pharmacy and Molecular Sciences, James Cook University, Townsville, QLD, 4811, Australia

    Beverley D. Glass

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  1. Deepa S. Maharaj
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  2. Beverley D. Glass
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  3. Santy Daya
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Correspondence to Santy Daya.

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Maharaj, D.S., Glass, B.D. & Daya, S. Melatonin: New Places in Therapy. Biosci Rep 27, 299–320 (2007). https://doi.org/10.1007/s10540-007-9052-1

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