Any positive immunological effect is thought to be the result of melatonin acting on high-affinity receptors (MT1 and MT2) expressed in immunocompetent cells. Most existing data are based on small, incomplete trials. There have been few trials designed to judge the effectiveness of melatonin in disease treatment. An anti-inflammatory effect seems to be the most relevant. While it is known that melatonin interacts with the immune system, the details of those interactions are unclear. Melatonin metabolites generated from redox reactions include cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), and N1-acetyl-5-methoxykynuramine (AMK). The melatonin metabolites produced via the reaction of melatonin with reactive oxygen species or reactive nitrogen species also react with and reduce free radicals. 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. Melatonin occurs at high concentrations within mitochondrial fluid which greatly exceed the plasma concentration of melatonin. Via signal transduction through melatonin receptors, melatonin promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. In plants, melatonin works with other antioxidants to improve the overall effectiveness of each antioxidant. , and the reactive nitrogen species NO.In vitro, melatonin acts as a direct scavenger of oxygen radicals including OH Melatonin was first reported as a potent antioxidant and free radical scavenger in 1993. Also, as children become teenagers, the nightly schedule of melatonin release is delayed, leading to later sleeping and waking times. Human melatonin production decreases as a person ages. Human infants' melatonin levels become regular in about the third month after birth, with the highest levels measured between midnight and 8:00 am. In animals, melatonin plays an important role in the regulation of sleep–wake cycles. When the eyes do not receive light, melatonin is produced in the pineal gland and the human becomes tired. 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. 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. Melatonin receptors 1 and 2 are both G i/o-coupled GPCRs, although melatonin receptor 1 is also G q-coupled. 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). In addition to its role as a natural hormone and antioxidant, melatonin is used as a dietary supplement and medication in the treatment of sleep disorders such as insomnia and circadian rhythm sleep disorders. Mitochondria are the main cell organelles that produce the antioxidant melatonin, which indicates that melatonin is an "ancient molecule" that primarily provided the earliest cells protection from the destructive actions of oxygen. Its primary function is to defend against oxidative stress in plants and bacteria. Many of its effects are through activation of the melatonin receptors, while others are due to its role as an antioxidant. 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. It was subsequently discovered as a hormone released in the brain at night which controls the sleep–wake cycle in vertebrates. Lerner and colleagues in 1958 as a substance of the pineal gland from cow that could induce skin lightening in common frogs. Melatonin is a natural compound, specifically an indoleamine, produced by and found in different organisms including bacteria and eukaryotes.
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