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.

Graphical Abstract

中文翻译：

---

天然免疫抑制剂治疗慢性失眠，靶向 NLRP3/caspase-1/IL-1β 轴激活引起的炎症反应：独家综述

慢性失眠是一种炎症相关疾病，是多种疾病的重要病理基础，严重威胁人的身心健康。迄今为止，人们提出了许多假说来解释失眠的发病机制，其中炎症机制已成为科学关注的焦点。在这方面，本次专题综述的目的是评估天然化合物在治疗慢性失眠中的潜在益处，该化合物靶向核苷酸结合寡聚结构域（NOD）样受体-含吡啶蛋白3（NLRP3）/caspase-1 /IL-1β轴是炎症级联最重要的激活剂之一。数据表明，有可能引起炎症的化合物会诱发睡眠障碍，而炎症介质是调节神经元睡眠相关活动的关键分子。在失眠的炎症过程中，NLRP3在失眠发病机制中的作用逐渐被研究者认为。NLRP3 是一种细胞内传感器，可识别最广泛的病原体相关分子模式 (PAMP) 和危险相关分子模式 (DAMP)。鉴定并与损伤因子结合后，NLRP3 炎症小体被组装以激活 caspase-1 和 IL-1β。IL-1β 产生和分泌的增加可能与中枢神经系统生理睡眠失调有关。目前的独家综述报告了针对 NLRP3 炎症小体通路活性的天然化合物的潜在益处，并强调了 NLRP3 /caspase-1/IL-1β 可能作为控制炎症和改善慢性失眠症状的潜在治疗靶点的假设。

图形概要