Melatonin Ameliorates the Progression of Atherosclerosis via Mitophagy Activation and NLRP3 Inflammasome Inhibition

Ma, Sai; Chen, Jiangwei; Feng, Jing; Zhang, Ran; Fan, Min; Han, Dongyi; Li, Xiang; Li, Congye; Ren, Jun; Wang, Yabin; Cao, Feng

doi:10.1155/2018/9286458

Cited by 206 publications

(160 citation statements)

References 49 publications

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“…Similar results were obtained when these cells were incubated in the presence of IL‐1β and other cytokines . Since melatonin treatment of macrophages prevented the stimulatory effect of conditioned media on POMC expression in AtT‐20 corticotrophs, we suggest that by inhibiting the production of IL‐1β (by blocking inflammasome activation) or other cytokines by local macrophages, as previously demonstrated in RAW264.7 cells, melatonin could prevent the simulation of POMC/ACTH by pituitary corticotrophs in SRD‐treated rats. An additional effect of melatonin in preventing ROS‐dependent negative feed‐back regulation of glucocorticoids on corticotroph POMC production as described by Asaba et al could not be discarded.…”

Section: Discussionsupporting

confidence: 86%

Melatonin prevents early pituitary dysfunction induced by sucrose‐rich diets

Mercau

Calanni

Aranda

et al. 2019

Journal of Pineal Research

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While physiological levels of glucocorticoids are required to ensure proper functions of the body, consistently high levels may engender several deleterious consequences. We have previously shown an increase in the activity of the hypothalamic‐pituitary‐adrenal (HPA) axis in rats fed sucrose‐rich diets (SRD). The main goal of this study was to analyze the processes involved in the modulation of the pituitary production of ACTH by SRD, and to test melatonin as a possible therapeutic agent for the prevention of the HPA axis dysfunction. Male Wistar rats were fed standard chow and either SRD (30% sucrose in the drinking water) or plain water for three weeks. Melatonin was administered as subcutaneous pellets. Results showed that SRD treatment induced an increase in systemic ACTH and corticosterone levels and a decrease in melatonin levels. In the pituitary gland, we also detected an increase in the expression levels of proopiomelanocortin (POMC) that was accompanied by increased levels of: lipoperoxides, nitro‐tyrosine modified proteins, catalase, heme oxygenase‐1, interleukin‐1β mRNA, and by an increase in the tissue number of inflammatory cells (F4/80 and Iba‐1 positive cells). Melatonin treatment prevented all these systemic and pituitary changes as well as the increase in POMC expression induced by incubation of AtT‐20 corticotrophs with conditioned media obtained from stimulated macrophages. In conclusion, stimulation of POMC/ACTH production in rats fed a SRD could involve the generation of oxidative stress and inflammation in the pituitary gland. Melatonin treatment prevented these effects and normalized the activity of the HPA axis.

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Section: Discussionsupporting

confidence: 86%

Melatonin prevents early pituitary dysfunction induced by sucrose‐rich diets

Mercau

Calanni

Aranda

et al. 2019

Journal of Pineal Research

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“…Thus, it is necessary to inhibit pyroptosis by acting on NLRP3, preferably immediately in the lungs. The mechanisms of NLRP3 inhibition have been studied [38], and melatonin reported as NLRP3 inflammasome inhibitor [39]. On the model of bacterial pneumonia, LPS-induced ALI mouse model, it was shown that melatonin successfully inhibits pneumonia through interfering with NLRP3 inflammasome, protecting macrophages from pyroptosis [40].…”

Section: Coronavirus Activates Inflammasome and Causes Inflammation mentioning

confidence: 99%

Can melatonin reduce the severity of COVID-19 pandemic?

Shneider

Kudriavtsev

Vakhrusheva

2020

International Reviews of Immunology

146

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The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children don't suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients' health after the active phase of the infection is over. ARTICLE HISTORY

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“…Melatonin (N-acetyl-5-methoxytryptamine), which is synthesized by the pineal gland and many other organs, is a neuroendocrine hormone 28,29 that is involved in a wide range of physiological functions, including anti-inflammatory, 30,31 antidegenerative, 32,33 antioxidant, 34,35 immunomodulatory, 36,37 circadian rhythm regulation, 38 and cancer prevention activities. [39][40][41][42] Notably, recent studies have demonstrated that melatonin attenuates the inflammatory response by inhibiting NLRP3 inflammasome activation during the progression of atherosclerosis 43 and brain, 44 liver 45 and lung diseases. 46 Moreover, melatonin plays crucial roles in the IVDD process, including regulating NP cell proliferation, remodeling the ECM, 47 protecting vertebral endplate chondrocytes against apoptosis and calcification, 48 and preventing oxidative stress-induced NP cell apoptosis, 49 indicating a strong correlation between melatonin and IVDD.…”

Section: Introductionmentioning

confidence: 99%

Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop

et al. 2020

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The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin (IL)-1β, and is one of the main causes of intervertebral disc degeneration (IVDD). NLR pyrin domain containing 3 (NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model; moreover, NLRP3 inflammasome activation (NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus (NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species (mtROS) production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mtROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.

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Melatonin Ameliorates the Progression of Atherosclerosis via Mitophagy Activation and NLRP3 Inflammasome Inhibition

Cited by 206 publications

References 49 publications

Melatonin prevents early pituitary dysfunction induced by sucrose‐rich diets

Melatonin prevents early pituitary dysfunction induced by sucrose‐rich diets

Can melatonin reduce the severity of COVID-19 pandemic?

Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop

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