COVID-19: Melatonin as a potential adjuvant treatment

Life Sciences, Journal Year: 2020, Volume and Issue: 250, P. 117583 - 117583

Published: March 23, 2020

Language: Английский

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Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: July 2, 2019

Inflammation is a crucial component of various stress-induced responses that contributes to the pathogenesis major depressive disorder (MDD). Depressive-like behavior (DLB) characterized by decreased mobility and occurs in systemic infection induced Lipopolysaccharide (LPS) experimental animals considered as model exacerbation MDD. We assessed effects melatonin on behavioral changes inflammatory cytokine expression hippocampus mice LPS-induced DLB, well its NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation, oxidative stress pyroptotic cell death murine microglia vitro. Intraperitoneal 5 mg/kg dose LPS was used mimic depressive-like behaviors given at 500 mg / kg for 4 times with 6 hour intervals, starting 2 hours before administration. Behavioral assessment carried out 24 post-LPS injection tail suspension forced swimming tests. Additionally, hippocampal NLRP3 protein levels were estimated. Melatonin increased time DLB suppressed interleukin-1 (IL-1) cleavage hippocampus. Immunofluorescence staining tissue showed mainly expressed ionized calcium-binding adapter molecule 1 (Iba1) -positive microglia. Our results show prevents Adenosine triphosphate (ATP) activation vitro, evidenced inhibition expression, Apoptosis-associated speck-like containing CARD (ASC) speck formation, caspase-1 maturation secretion. inhibits pyroptosis, production mitochondrial cytosolic reactive oxygen species (ROS) nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) signaling. The beneficial associated erythroid 2–related (Nrf2) Silent information regulator homolog (SIRT1) which reversed Nrf2 siRNA SIRT1 inhibitor treatment.

Language: Английский

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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(18), P. 4472 - 4472

Published: Sept. 10, 2019

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed the elderly population. Inflammaging associated over-abundance reactive oxygen species cell, which can lead to oxidation and damage cellular components, increased inflammation, activation cell death pathways. This review focuses on inflammaging its contribution various age-related diseases such cardiovascular disease, cancer, neurodegenerative diseases, obstructive pulmonary diabetes, rheumatoid arthritis. Recently published mechanistic details roles will also be discussed. Advancements potential treatments ameliorate oxidative stress, consequently, reduce morbidity explored.

Language: Английский

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Neuroinflammation in Alzheimer’s Disease

Biomedicines, Journal Year: 2021, Volume and Issue: 9(5), P. 524 - 524

Published: May 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Language: Английский

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The role of cellular senescence in female reproductive aging and the potential for senotherapeutic interventions

Human Reproduction Update, Journal Year: 2021, Volume and Issue: 28(2), P. 172 - 189

Published: Nov. 11, 2021

Advanced maternal age is associated with decreased oocyte quantity and quality as well uterine placental dysfunctions. These changes lead to infertility, pregnancy complications birth defects in the offspring. As mean of giving increasing worldwide, prevention age-associated infertility complications, along more frequent use ART, become extremely important. Currently, significant research being conducted unravel mechanisms underlying female reproductive aging. Among potential involved, recent evidence has suggested a contributing role for cellular senescence, state irreversible growth arrest characterized by hypersecretory pro-inflammatory phenotype. Elucidating senescence aging holds developing novel less invasive therapeutic measures prevent or even reverse increase offspring wellbeing.

Language: Английский

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Inflammaging: Implications in Sarcopenia

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 15039 - 15039

Published: Nov. 30, 2022

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes contemporary demand. the elderly, sterile, chronic low-grade systemic inflammation known as “inflammaging” linked with many age-associated diseases. Considering sarcopenia loss of strength mass skeletal muscle related to aging, correlations between these two terms have been proposed. Better knowledge immune system players would help elucidate their implications sarcopenia. Characterizing activators damage sensors downstream effectors explains inference performance. Sarcopenia has also diseases such diabetes, metabolic syndrome obesity. Implications inflammatory signals from negatively affect muscle. Autophagic mechanisms are closely inflammasome, autophagy eliminates stress signaling sent by organelles, but acts an immunomodulatory function affecting cells cytokine release. The use melatonin, antioxidant, ROS scavenger modulator, or senotherapeutic compounds targeting senescent could represent strategies counteract inflammation. This review aims present factors regulating inflammaging major order understand molecular involved

Language: Английский

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Protective Role of Melatonin and Its Metabolites in Skin Aging

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1238 - 1238

Published: Jan. 22, 2022

The skin, being the largest organ in human body, is exposed to environment and suffers from both intrinsic extrinsic aging factors. skin process characterized by several clinical features such as wrinkling, loss of elasticity, rough-textured appearance. This complex accompanied with phenotypic functional changes cutaneous immune cells, well structural disturbances extracellular matrix components collagens elastin. Because health considered one principal factors representing overall “well-being” perception “health” humans, anti-aging strategies have recently been developed. Thus, while fundamental mechanisms regarding are known, new substances should be for introduction into dermatological treatments. Herein, we describe melatonin its metabolites potential “aging neutralizers”. Melatonin, an evolutionarily ancient derivative serotonin hormonal properties, main neuroendocrine secretory product pineal gland. It regulates circadian rhythmicity also exerts anti-oxidative, anti-inflammatory, immunomodulatory, anti-tumor capacities. intention this review summarize within aging, research advances on molecular leading these changes, impact melatoninergic anti-oxidative system controlled metabolites, targeting prevention or reversal aging.

Language: Английский

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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

Antioxidants, Journal Year: 2022, Volume and Issue: 11(7), P. 1224 - 1224

Published: June 22, 2022

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial protective several physiological processes, excessive senescent burden has been involved various pathological conditions including aging, tissue dysfunction chronic diseases. Oxidative stress (OS) can drive due a loss balance between pro-oxidant stimuli antioxidant defences. Therefore, the identification characterization compounds capable preventing or counteracting phenotype major interest. However, despite considerable number studies, comprehensive overview main molecules OS-induced still lacking. Here, besides brief description molecular mechanisms implicated OS-mediated we review discuss role enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur nitrogen non-protein molecules, minerals, flavonoids, non-flavonoids with anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.

Language: Английский

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Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Nutrients, Journal Year: 2022, Volume and Issue: 14(19), P. 3934 - 3934

Published: Sept. 22, 2022

Melatonin has become a popular dietary supplement, most known as chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer’s disease, multiple sclerosis, fertility, PCOS, many other conditions, combined with COVID-19 pandemic, led to greater awareness of melatonin because its ability act potent antioxidant, immune-active agent, mitochondrial regulator. There are distinct similarities between vitamin D in depth breadth their impact on health. Both hormones, affect systems through immune-modulating, anti-inflammatory functions, found skin, responsive sunlight darkness. In fact, there may be widespread concern about deficiency “sunlight deficiency” reduced secretion result “darkness from overexposure artificial blue light. The trend toward use supplements resulted safety, especially higher doses, long-term use, application certain populations (e.g., children). This review aims evaluate recent data melatonin’s mechanisms, clinical uses beyond sleep, safety concerns, thorough summary therapeutic considerations concerning supplementation, including different formats available (animal, synthetic, phytomelatonin), dosing, timing, contraindications, nutrient combinations.

Language: Английский

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Ameliorating Mitochondrial Dysfunction of Neurons by Biomimetic Targeting Nanoparticles Mediated Mitochondrial Biogenesis to Boost the Therapy of Parkinson's Disease

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: May 18, 2023

Abstract Mitochondrial dysfunction of neurons is the core pathogenesis incurable Parkinson's disease (PD). It crucial to ameliorate mitochondrial for boosting therapy PD. Herein, remarkable promotion biogenesis and improve treatment PD by using mitochondria‐targeted biomimetic nanoparticles, which are Cu 2‐ x Se‐based nanoparticles functionalized with curcumin wrapped DSPE‐PEG 2000 ‐TPP‐modified macrophage membrane (denoted as CSCCT NPs), reported. These can efficiently target mitochondria damaged in an inflammatory environment, mediate signaling pathway NAD + /SIRT1/PGC‐1 α /PPAR γ /NRF1/TFAM alleviate 1‐methyl‐4‐phenylpyridinium (MPP )‐induced neuronal toxicity. They reduce reactive oxygen species, restore potential (MMP), protect integrity respiratory chain, via promoting biogenesis, synergistically motor disorders anxiety behavior 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mice. This study demonstrates that targeting has a great mitochondria‐related diseases.

Language: Английский

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