MELATONIN: from synthesis to the mechanism of action
MECHANISM OF ACTION
Synchronization of biological rhythms
The biological rhythms of the organism are regulated by a sort of "biological clock", located in the hypothalamus: the Suprachiasmatic Nucleus. The most evident examples of this "clock" are: the variation of blood pressure and that of body temperature, the regulation of sleep / wakefulness and hunger / thirst, the regulation of the tone and movements of the smooth muscles of the organs of the digestive system, urinary system and the secretory activity of the glands. All of these listed above fall within circadian rhythms, but gestation, childbirth, breastfeeding or development are also subject to this neuronal control. The light / dark alternation is recognized as the main factor that regulates circadian rhythms and melatonin is the effector of this system.
Body temperature modulator
Body temperature is controlled by the body's thermoregulatory center located inside the hypothalamus. This center works like a thermostat, which sets an average core body temperature whose values are around 37 ° C ± 0.5 ° C - records the variations and determines the adjustments. The change in body temperature follows a circadian rhythm and therefore melatonin affects it. Melatonin is able to reduce body temperature by about 0.3 ° C (40% of the circadian variation in temperature). The hypothermic effect of Melatonin has been highlighted with its diurnal administration, that is, when it is not normally produced: an effect similar to the physiological one is found. If administered during the night, when endogenous melatonin is normally produced, melatonin does not exert an additional hypothermic effect.
The best known physiological action, and perhaps still the most exploited of melatonin, is the effect it has on sleep. The effect of the substance was evaluated on various components of sleep. The greatest and most consistent effect is certainly that exerted on the propensity to fall asleep, which shows a variation over the 24 hours: it rises suddenly after 8 pm, simultaneously with the onset of melatonin secretion, to reach a maximum at the melatonin peak and the lowest levels of body temperature.
Natural antiplatelet agent
Melatonin is the most physiological antiplatelet agent, guaranteeing the maintenance of the properties of the blood and the trophism of the vessel walls. This action can also be considered biorhythmically regulated and be more accentuated during the night
Natural defense of free radicals
Melatonin exerts an antioxidant action as a free molecule and it is of great importance that it exerts this action in all intracellular compartments. This is due to its lipophilic nature which makes it able to cross all biological barriers and spread to every compartment of the cell. By entering the cell as a free molecule, melatonin is able to exert a function of neutralization of free radicals: by donating electronic groups to free radicals it makes them less reactive and therefore less toxic. By reacting with a free radical, melatonin is oxidized and forms an indole cationic radical. Subsequently, the indole radical, reacting with a superoxide radical anion (O2ˉ), forms a stable and non-toxic product, 5-methoxy-N-acetyl-N-formyl-kynuramine. The scavenger action of melatonin has also proved efficient towards the peroxyl radical (ROOˉ), a radical species that is generated during lipid peroxidation and which propagates a chain reaction that induces massive lipid destruction in cell membranes. Melatonin is extremely powerful in protecting against damage caused by free radicals also induced by various external stimuli. Thus, DNA damage resulting from exposure to carcinogenic chemicals or ionizing radiation is markedly reduced when melatonin is co-administered
The interaction between the nervous, endocrine and immune systems has long been known, and is an integral part of a discipline called neuroimmunomodulation. It is established that the immune and central nervous systems are linked both anatomically and functionally and that different signal molecules and receptors are common to both. The immunimodulatory action of melatonin is mediated by receptors located both at the membrane and nuclear level
We can therefore basically distinguish two functions of melatonin in relation to the immune system: an antigen-dependent action, where melatonin produces activation of the immune system by strengthening the functions of T-helper and the production of cytokines, and an antigen-independent action. at the hematopoietic level where it maintains immune homeostasis.
Melatonin intervenes in the control of neurotransmission at the level of the neuronal membranes of the nervous system, resulting in a stabilizing action of electrical activity.
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