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Natural Immunosuppressants as a Treatment for Chronic Insomnia Targeting the Inflammatory Response Induced by NLRP3/caspase-1/IL-1β Axis Activation: A Scooping Review

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Abstract

Chronic insomnia is an inflammatory-related disease with an important pathological basis for various diseases which is a serious threat to a person’s physical and mental health. So far, many hypotheses have been proposed to explain the pathogenesis of insomnia, among which inflammatory mechanisms have become the focus of scientific attention. In this regard, the aim of the present scooping review is to evaluate the potential benefits of natural compounds in treatment of chronic insomnia targeting nucleotide-binding oligomerization domain (NOD)-like receptor-pyrin-containing protein 3 (NLRP3)/caspase-1/IL-1β axis as one of the most important activators of inflammatory cascades. The data show that compounds that have the potential to cause inflammation induce sleep disorders, and that inflammatory mediators are key molecules in regulating the sleep-related activity of neurons. In the inflammatory process of insomnia, the role of NLRP3 in the pathogenesis of insomnia has been gradually considered by researchers. NLRP3 is an intracellular sensor that recognizes the widest range of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). After identification and binding to damage factors, NLRP3 inflammasome is assembled to activate the caspase-1 and IL-1β. Increased production and secretion of IL-1β may be involved in central nervous system dysregulation of physiological sleep. The current scooping review reports the potential benefits of natural compounds that target NLRP3 inflammasome pathway activity and highlights the hypothesis which NLRP3 /caspase-1/IL-1β may serve as a potential therapeutic target for managing inflammation and improving symptoms in chronic insomnia.

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Acknowledgements

The financial supports of Kermanshah University of Medical Sciences (Grant No. 980130) are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Zahra Aghelan & Somayeh Pashaee

  2. Department of Laboratory Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Seyed Hosein Abtahi

  3. Department of Clinical Biochemistry, Faculty of Medicine, Shahid Behehshti University of Medical Sciences, Tehran, Iran

    Saeed Karima

  4. Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Habibolah Khazaie

  5. Medical Biology Research Center, Research Institute for Health Technology, Kermanshah University of Medical Sciences, Nurse Street, Kermanshah, 6714415185, Iran

    Mohammad Ezati & Reza Khodarahmi

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Aghelan, Z., Pashaee, S., Abtahi, S.H. et al. Natural Immunosuppressants as a Treatment for Chronic Insomnia Targeting the Inflammatory Response Induced by NLRP3/caspase-1/IL-1β Axis Activation: A Scooping Review. J Neuroimmune Pharmacol 18, 294–309 (2023). https://doi.org/10.1007/s11481-023-10078-7

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