Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle.
In vertebrates, melatonin is involved in synchronizing circadian rhythms, including sleep–wake timing and blood pressure regulation, and in control of seasonal rhythmicity including reproduction, fattening, moulting and hibernation. Many of its effects are through activation of the melatonin receptors, while others are due to its role as an antioxidant. In plants, it functions to defend against oxidative stress. It is also present in various foods.
Melatonin was discovered in 1958.
In addition to its role as a natural hormone, melatonin is used as a dietary supplement and medication in the treatment of sleep disorders such as insomnia and circadian rhythm sleep disorders; for information on melatonin as a supplement and medication, see the melatonin (supplement/medication) article.
Biological activity[edit]
In humans, melatonin is a full agonist of melatonin receptor 1 (picomolar binding affinity) and melatonin receptor 2 (nanomolar binding affinity), both of which belong to the class of G-protein coupled receptors (GPCRs). Melatonin receptors 1 and 2 are both Gi/o-coupled GPCRs, although melatonin receptor 1 is also Gq-coupled. Melatonin also acts as a high-capacity free radical scavenger within mitochondria which also promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase via signal transduction through melatonin receptors.
Biological functions
When eyes receive light from the sun, the pineal gland's production of melatonin is inhibited and the hormones produced keep the human awake. When the eyes do not receive light, melatonin is produced in the pineal gland and the human becomes tired.
Circadian rhythm
In animals, melatonin plays an important role in the regulation of sleep–wake cycles. Human infants' melatonin levels become regular in about the third month after birth, with the highest levels measured between midnight and 8:00 am.Human melatonin production decreases as a person ages. Also, as children become teenagers, the nightly schedule of melatonin release is delayed, leading to later sleeping and waking times.
Antioxidant
Melatonin was first reported as a potent antioxidant and free radical scavenger in 1993. In vitro, melatonin acts as a direct scavenger of oxygen radicals including OH•, O2−•, and the reactive nitrogen species NO•.In plants, melatonin works with other antioxidants to improve the overall effectiveness of each antioxidant.Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Via signal transduction through melatonin receptors, melatonin promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase.
Melatonin occurs at high concentrations within mitochondrial fluid which greatly exceed the plasma concentration of melatonin. Due to its capacity for free radical scavenging, indirect effects on the expression of antioxidant enzymes, and its significant concentrations within mitochondria, a number of authors have indicated that melatonin has an important physiological function as a mitochondrial antioxidant.
The melatonin metabolites produced via the reaction of melatonin with reactive oxygen species or reactive nitrogen species also react with and reduce free radicals. Melatonin metabolites generated from redox reactions include cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), and N1-acetyl-5-methoxykynuramine (AMK).
Immune system
While it is known that melatonin interacts with the immune system,the details of those interactions are unclear. An anti-inflammatory effect seems to be the most relevant. There have been few trials designed to judge the effectiveness of melatonin in disease treatment. Most existing data are based on small, incomplete trials. Any positive immunological effect is thought to be the result of melatonin acting on high-affinity receptors (MT1 and MT2) expressed in immunocompetent cells. In preclinical studies, melatonin may enhance cytokine production, and by doing this, counteract acquired immunodeficiences. Some studies also suggest that melatonin might be useful fighting infectious disease including viral, such as HIV, and bacterial infections, and potentially in the treatment of cancer.
Weight regulation
A possible mechanism by which melatonin may regulate weight gain is through its inhibitory effect on leptin. Leptin acts as a long-term indicator of energy status in the human body.[31] By suppressing leptin's actions outside of waking hours, melatonin may help restore leptin sensitivity during the daytime by alleviating leptin resistance.
Medical use
Melatonin is used as a medication in the treatment of sleep disorders such as insomnia and circadian rhythm sleep disorders like delayed sleep phase disorder, jet lag disorder, and shift work disorder. Besides melatonin, certain synthetic melatonin receptor agonists like ramelteon, tasimelteon, and agomelatine are also used in medicine
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