摘要
Inflammasomes是具有核苷酸结合结构域和富含亮氨酸重复组成成员以及pyrin和HIN结构域家族的多蛋白复合物。炎症小体主要由细胞质传感器分子,如NLRP3,接头细胞凋亡相关的斑点状蛋白质含有胱天蛋白酶募集域)蛋白以及效应子胱天蛋白酶原-1组成。炎症细胞调节半胱天冬酶-1激活,导致白细胞介素-1β和白细胞介素-18的分泌。炎症性活化与炎症相关的感染,应激或其他免疫学信号相关。NLRP3炎症细胞在免疫调节,炎症受体 - 配体相互作用,微生物相关分子模式,危险以及病原体相关分子模式中的病理生理作用已经在近几年得到证实。此外,在临床前和临床研究中已经证明了炎症小体在涉及细胞因子和趋化因子炎症反应的外周和中枢神经系统中的作用。对炎症相关途径的分子调控的理解对于药物设计和递送至关重要。使用天然产物作为替代疗法正在获得关注,因为易于获取和成本效益。被称为植物化学物质的许多草药提取物及其生物活性成分显示出在NLRP3炎症反应途径介导的炎症反应中是有效的。为了了解植物化学物质和炎性体在分子水平上的相互作用,开发有效药物至关重要,可在临床环境中进一步评估。因此,本综述对所有在炎症实验动物模型中或在调节NLRP3炎症小体介导的途径以减轻炎症反应的永生化人/动物细胞系中评估的所有植物化学物质进行了广泛的介绍,希望植物化学物质可以提供这种途径调节 另一类药物在装置中以及针对NLRP3炎性体的天然产物的新型分子机制。
关键词: 草药,炎症,炎症,白介素-1β,NLRP3,植物化学物质,药用植物,炎性疾病。
Current Medicinal Chemistry
Title:Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases
Volume: 24 Issue: 16
关键词: 草药,炎症,炎症,白介素-1β,NLRP3,植物化学物质,药用植物,炎性疾病。
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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Cite this article as:
Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases, Current Medicinal Chemistry 2017; 24 (16) . https://dx.doi.org/10.2174/0929867324666170227121619
DOI https://dx.doi.org/10.2174/0929867324666170227121619 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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