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Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome

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Abstract

Melatonin is a hormone of the pineal gland that contributes to the regulation of physiological activities, such as sleep, circadian rhythm, and neuroendocrine processes. Melatonin is found in several plants and has pharmacological activities including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, and neuroprotective. It also has shown therapeutic efficacy in treatment of cancer and diabetes. Melatonin affects several molecular pathways to exert its protective effects. The NLRP3 inflammasome is considered a novel target of melatonin. This inflammasome contributes to enhanced level of IL-1β, caspase-1 activation, and pyroptosis stimulation. The function of NLRP3 inflammasome has been explored in various diseases, including cancer, diabetes, and neurological disorders. By inhibiting NLRP3, melatonin diminishes inflammation and influences various molecular pathways, such as SIRT1, microRNA, long non-coding RNA, and Wnt/β-catenin. Here, we discuss these molecular pathways and suggest that melatonin-induced inhibition of NLRP3 should be advanced in disease therapy

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Abbreviations

NLRP3:

NOD-like receptor protein 3

PRRs:

pattern recognition receptors

PAMPs:

pathogen-associated molecular patterns

DAMPs:

damage-associated molecular patterns

TLRs:

Toll-like receptors

CLRs:

C-type lectin receptors

PLR:

RIG-I-like receptor

NLR:

NOD-like receptor

DCs:

dendritic cells

PYD:

PYRIN domain

NACHT:

NOD nucleotide-binding domain

LPR:

leucine-rich repeat

ROS:

reactive oxygen species

IL:

interleukin

NF-κB:

nuclear factor-κB

FADD:

FAS-associated death domain protein

ATP:

adenosine triphosphate

NDs:

neurological disorders

DM:

diabetes mellitus

TIDM:

type I DM

TIIDM:

type II DM

AGEs:

advanced glycation end products

AMPK:

AMP-activated protein kinase

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

Aβ:

amyloid beta

ALS:

amyotrophic lateral sclerosis

NFTs:

neurofibrillary tangles

LSCC:

laryngeal squamous cell carcinoma

Nrf2:

nuclear factor erythroid 2-related factor 2

HO-1:

heme oxygenase-1

NQO1:

NADPH dehydrogenase quinone 1

I/R:

ischemic/reperfusion

HSP70:

heat shock protein 70

MST1:

mammalian sterile 20-like kinase 1

MIEF1:

mitochondrial/elongation factor 1

TNF-α:

tumor necrosis factor-α

FKBP3:

FK506-binding protein 3

LPS:

lipopolysaccharide

MAPK:

mitogen-activated protein kinase

ER:

endoplasmic reticulum

IVDD:

intervertebral disc degeneration

MMP-3:

matrix metalloproteinase-3

STAT3:

signal transducer and activator of transcription 3

LBP:

low back pain

NF:

nucleus pulposus

AF:

annulus fibrosus

IVD:

intervertebral disc

NAMPT:

nicotine-amide phosphoribosyl transferase

CpG-ODN:

CpG oligodeoxynucleotide

ECs:

endothelial cells

ED:

endothelial dysfunction

AS:

atherosclerosis

MDD:

major depressive disorder

LN:

lupus nephritis

SLE:

systemic lupus erythrematosus

SCI:

spinal cord injury

UPR:

unfold protein response

TXNIP:

thioredoxin-interacting protein

COPD:

chronic obstructive pulmonary disease

OCN:

osteocalcin

SAH:

subarachnoid hemorrhage

BBB:

blood-brain barrier

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Authors and Affiliations

  1. Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956, Istanbul, Turkey

    Milad Ashrafizadeh

  2. Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956, Istanbul, Turkey

    Milad Ashrafizadeh

  3. Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Masoud Najafi

  4. Department of Basic Science, Faculty of Veterinary Medicine Faculty, Islamic Azad Branch, University of Shushtar, Shushtar, Khuzestan, Iran

    Nasim Kavyiani

  5. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Reza Mohammadinejad

  6. Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran

    Tahereh Farkhondeh

  7. Faculty of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran

    Tahereh Farkhondeh

  8. Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

    Saeed Samarghandian

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  1. Milad Ashrafizadeh
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  2. Masoud Najafi
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  3. Nasim Kavyiani
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  4. Reza Mohammadinejad
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  5. Tahereh Farkhondeh
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  6. Saeed Samarghandian
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Contributions

Study conception and design: MA, MN, and SS

Acquisition of data: MA, NK, RM, and TF

Drafting of the manuscript: MA, MN, NK, and RM

Critical revision: SS

Final approval: All authors

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Correspondence to Saeed Samarghandian.

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Ashrafizadeh, M., Najafi, M., Kavyiani, N. et al. Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome. Inflammation 44, 1207–1222 (2021). https://doi.org/10.1007/s10753-021-01428-9

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  • DOI: https://doi.org/10.1007/s10753-021-01428-9

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