Physiological and pharmacological roles of melatonin in the pathophysiological components of cellular injury after ischemic stroke

Abstract

Apart from its metabolic or physiological functions, melatonin has a potent cytoprotective activity in the physiological and pathological conditions. It is synthetized by the pineal gland and released into the blood circulation but particularly cerebrospinal fluid in a circadian manner. It can also easily diffuse through cellular membranes due its small size and lipophilic structure. Its cytoprotective activity has been linked to its potent free radical scavenger activity with the desirable characteristics of a clinically- reliable antioxidant. Melatonin detoxifies oxygen and nitrogen-based free radicals and oxidizing agents, including the highly toxic hydroxyl-and peroxynitrite radicals, initiating cellular damage. However, the cytoprotective activity of melatonin is complex and cannot be solely limited to its free radical scavenger activity. It regulates cellular signaling pathways through receptor– dependent and independent mechanisms. Most of these downstream molecules, such as PI3K/AKT pathway components, also contribute to the cytoprotective effects of melatonin. In this term, melatonin is a promising molecule for the treatment of neurodegenerative disorders, such as ischemic stroke, which melatonin reduces ischemic brain injury in animal models of ischemic stroke. It regulates also circadian rhythm proteins after ischemic stroke, playing roles in cellular survival. In this context, present article summarizes the possible role of melatonin in the pathophysiological events after ischemic stroke.

A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality via Regulating Brain Electrochemical Activity

“…Here, we observed that iNOS levels were enhanced after sole caffeine injection, similar to the previous results, while L -theanine and Mg-T injection after caffeine administration recovered that effect and reversed the increased iNOS levels. Given that hypoxic conditions such as stroke induce synthesis of NO by iNOS and this leads to exacerbation of the injury ( 64 ), Mg- L -theanine compounds may help reduction of inflammation by their anti-inflammatory role.…”

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

“…Melatonin, an endogenous regulator, is a metabolite of tryptophan released from the pineal gland ( 213 ). It is involved in numerous physiological and pathophysiological processes including antioxidant ( 214 ), anti-apoptotic, and anti-inflammatory effects ( 215 ). Melatonin is of neuroprotective effect, which reduces infarct volume, lowers brain edema, and increases neurological scores.…”

Melatonin Protects Against Ischemic Brain Injury by Modulating PI3K/AKT Signaling Pathway via Suppression of PTEN Activity

“…A multitude of different pathways have been associated with melatonin's protection on neurological damage, including maintaining Ca 2þ homeostasis (Onaolapo et al, 2019), decreasing oxidative stress (Watson et al, 2016), and attenuating endoplasmic reticulum stress (Lin et al, 2018). Melatonin was reported to play important roles in the pathophysiological components of cellular injury after ischemic stroke via modulating oxidative stress, mitochondria, apoptosis, inflammatory response, melatonin receptors 1/2, circular RNA in ischemic injury (Kilic et al, 2020). For example, in a focal cerebral ischemic injury rat model, melatonin reduced brain infarction associated with sequentially rescued neuronal apoptosis and attenuated neuroinflammatory response by modulating oxidative stress signaling (NF-jB/COX2/iNOS) and enhancing anti-oxidative systems such as Nrf2/HO-1/Trx (Ling et al, 2020).…”