Anti-inflammatory effects of Melatonin: A mechanistic review

Abstract

N-acetyl-5-methoxy-tryptamine (melatonin) is a natural substance produced both by plants, as a secondary metabolite, and animals, by the pineal gland and other tissues. In humans, melatonin participates in numerous functions including the regulation of mood, sleep, reproduction, promotion of immunomodulation, antioxidant defense and as an anti-inflammatory agent. The anti-inflammatory activity of melatonin could yield beneficial effects on intake, particularly against the chronic inflammation which underlies many chronic diseases. This review aims to provide an assessment of the literature data on the anti-inflammatory activity of melatonin, with a particular focus on the mechanisms responsible for this behavior. We can conclude that many in vitro studies and in vivo studies in experimental animal model systems show that melatonin exerts anti-inflammatory activity in a number of chronic diseases which affect different organs in different circumstances. Clinical trials, however, often fail to reach positive results and are thus far inconclusive. Thus, in the future, long-term well-designed investigations on melatonin-rich foods or melatonin food supplements could provide valuable information towards public health recommendations on melatonin, taking into account both the nature of the compound and the optimal dose, for protection from long-term inflammation linked to chronic diseases.

Effects of the drug combination memantine and melatonin on impaired memory and brain neuronal deficits in an amyloid-predominant mouse model of Alzheimer's disease

“…It is thought that memantine‐mediated suppression of oxidative stress underlies its anti‐inflammatory effects . It is well documented that melatonin possesses anti‐inflammatory properties, based generally on its antioxidant action (for review). Previous studies have established the ability of melatonin to inhibit nuclear factor‐kappa B (NF‐κB) and cyclooxygenase (COX)‐2, to prevent activated microglia‐induced production of proinflammatory cytokines and to reduce Aβ‐induced secretion of interleukins IL1‐β and IL‐6 in transgenic mouse models thereby protecting the brain …”

Melatonin and Its Protective Role against Biotic Stress Impacts on Plants

“…Many studies have shown that melatonin can play a key role in plant protection against biotic stress. melatonin has been reported to have immunomodulatory, antioxidant, anti-inflammatory, and neuroprotective activities in animals [31][32][33][34], so it can be applied as an effective therapeutic substitute for the suppression of microbial diseases. On the other hand, recently, many important findings have shown the beneficial effect of melatonin in plant-pathogen interaction.…”

“…Also, the strong inhibitory action of melatonin against Mycobacterium tuberculosis (H37Rv strain) was revealed after application of a 10 µM concentration; however, the combined application of melatonin with isoniazid inhibited the growth of bacteria three to four times more than any compound alone [53]. Besides its ability to potentiate immune responses, additional explanations have been provided to clarify the mechanism of melatonin's antibacterial action in animals, including cellular cAMP and Ca 2+ regulation, reduction of intracellular substrates, free radical formation, and binding to the bacterial cell wall, which causes cytoderm destabilization [32][33][34][35][36][37][38][52][53][54]. In plant-bacteria interaction, melatonin has presented effective antibacterial activities against phytobacterial pathogens.…”

Dysautonomia and Headache in the Pediatric Population

“…36 This step also includes nutraceuticals such as riboflavin (B2), magnesium, and coenzyme Q10 for migraine patients as well as vitamin B12, liquorice root, and vitamin C for POTS patients. 35,42,48 It also may counteract tachycardia in POTS patients. 35,42,48 It also may counteract tachycardia in POTS patients.…”

“…37,[44][45][46] Additionally, there is evidence that melatonin is beneficial for both migraine and POTS patients as it improves sleep and has antiinflammatory properties. 35,42,48 It also may counteract tachycardia in POTS patients. 35 While all of these complementary therapies are potential options for POTS and migraine patients alike, physical therapy and CBT are the most beneficial when headaches and dysautonomias are seen simultaneously.…”