Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases

炎症体 吡喃结构域 目标2 生物 半胱氨酸蛋白酶1 效应器 炎症 先天免疫系统 细胞生物学 信号转导衔接蛋白 信号转导 免疫学 免疫系统
作者
Sadaf Jahan,Dipak Kumar,Swati Chaturvedi,Mamunur Rashid,Muhammad Wahajuddin,Yasir Akhtar Khan,Sameer N. Goyal,Chandragouda R. Patil,Mohanraj Rajesh,Sandeep B. Subramanya,Shreesh Ojha
出处
期刊:Current Medicinal Chemistry [Bentham Science]
卷期号:24 (16) 被引量:32
标识
DOI:10.2174/0929867324666170227121619
摘要

Inflammasomes are multiprotein complexes having nucleotide-binding domain and leucine-rich repeat consisting members along with pyrin and HIN domain family. An inflammasome mainly consists of cytoplasmic sensor molecule, such as NLRP3, the adaptor apoptosisassociated speck-like protein containing caspase recruitment domain) protein along with effector procaspase-1. The inflammasome regulates caspase-1 activation, resulting in secretion of interleukin- 1β and interleukin-18. The inflammasome activation is linked with infection, stress, or other immunological signals involved in inflammation. The pathophysiological role of NLRP3 inflammasome in immune regulation, inflammatory receptor-ligand interactions, microbial-associated molecular patterns, danger as well as pathogen associated molecular patterns has been demonstrated in last few years. Furthermore, the role of the inflammasome in peripheral and central nervous system involved with cytokine and chemokine inflammatory responses has been demonstrated in preclinical and clinical studies. The understanding of molecular regulation of inflammasome associated pathways is crucial for drug design and delivery. The use of natural product as an alternate therapy is gaining focus because of easy access and cost effectiveness. A number of herbal extracts and its bioactive constituents known as phytochemicals have shown to be effective in inflammatory response mediated by NLRP3 inflammasomes pathways. To understand the interaction of phytochemicals and inflammasome at the molecular level, it is vital to develop effective drugs that can be evaluated further in the clinical settings. Therefore, this review renders an extensive account of all the phytochemicals which are evaluated either in inflammatory experimental animal models or in immortalized human/animal cell lines that modulate NLRP3 inflammasome mediated pathways to mitigate inflammatory responses with the hope that this pathway modulation by phytochemicals may provide a another class of drugs in the armamentarium as well as novel molecular mechanism of natural products targeting NLRP3 inflammasome.
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