Melatonin alleviates intestinal injury, neuroinflammation and cognitive dysfunction caused by intestinal ischemia/reperfusion

Yang, Bo; Li-yin, Zhang; Chen, Ye; Bai, Yiping; Jia, Jing; Feng, Jianguo; Liu, Ke-Xuan; Zhou, Jun

doi:10.1016/j.intimp.2020.106596

Cited by 35 publications

(29 citation statements)

References 46 publications

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“…Similar protection was obtained with the antioxidant N -acetylcysteine, which may indicate a role of ROS scavenging [ 34 ]. The prevention of microglial inflammasome activation may be largely explained by the downregulation of TLR4 (toll-like receptor 4) [ 35 , 36 , 37 , 38 ] and its adapter protein MyD88 (myeloid differentiation factor 88) [ 36 ], effects that have been observed in very different models and under various conditions. However, reduced TLR4-dependent signaling may also occur upon the prevention of HMGB1 (high mobility group box 1) release, an alarmin that activates TLR4, as reported for LPS-treated BV2 microglial cells [ 39 ].…”

Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

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Section: Melatonin Suppresses Proinflammatory and Favors Anti-inflammatory Signalingmentioning

confidence: 99%

Melatonin and Microglia

Hardeland

2021

IJMS

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“…Indeed, many studies have reported the protective effects of melatonin on tissue injuries caused by oxidative stress. These include ischemia/reperfusion induced injuries of brain, lungs, heart, intestine, testes and skeletal muscle as well as hypoxia-caused tissue and organ damages [ 102 , 103 , 104 , 105 , 106 , 107 ]. The protective effects of melatonin are largely associated with its activity on mitochondria.…”

Section: Mitochondria and Melatoninmentioning

confidence: 99%

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Tan¹,

Hardeland

2020

Molecules

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Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen’s spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host’s tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

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“…In rats affected by intestinal I/R injury, melatonin alleviated cognitive impairment and decreased proinflammatory factors, such as tumor necrosis factor-α, IL-6 and interleukin-1β, along with attenuating oxidative stress in the brain, blood serum and intestinal tissue. Additionally, melatonin inhibited apoptosis and microglial hyperactivity in brain tissue [ 75 ]. Notably, melatonin restores hippocampal neurogenesis in mice treated with cuprizone by enhancing BDNF and increasing CREB phosphorylation [ 76 ].…”

Section: Novel Evidence Supporting Melatonin As An Effective Theramentioning

confidence: 99%

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

et al. 2020

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Secreted by the pineal gland to regulate the circadian rhythm, melatonin is a powerful antioxidant that has been used to combat oxidative stress in the central nervous system. Melatonin-based therapies have been shown to provide neuroprotective effects in the setting of ischemic stroke by mitigating neuroinflammation and accelerating brain tissue restoration. Melatonin treatment includes injection of exogenous melatonin, pineal gland grafting and melatonin-mediated stem cell therapy. This review will discuss the current preclinical and clinical studies investigating melatonin-based therapeutics to treat stroke.

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Melatonin alleviates intestinal injury, neuroinflammation and cognitive dysfunction caused by intestinal ischemia/reperfusion

Cited by 35 publications

References 46 publications

Melatonin and Microglia

Melatonin and Microglia

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Melatonin—A Potent Therapeutic for Stroke and Stroke-Related Dementia

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