Zou Jian, Wang Sheng-Peng, Wang Yi-Tao, Wan Jian-Bo
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China.
Pharmacol Res. 2021 Feb;164:105388. doi: 10.1016/j.phrs.2020.105388. Epub 2020 Dec 21.
The past decades have witnessed significant progress in understanding the process of sterile inflammation, which is dependent on a cytosolic complex termed the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Activation of NLRP3 inflammasome requires two steps, including the activation of Toll-like receptor (TLR) by its ligands, resulting in transcriptional procytokine and inflammasome component activation, and the assembly and activation of NLRP3 inflammasome triggered by various danger signals, leading to caspase-1 activation, which could subsequently cleave procytokines into their active forms. Metabolic disorders, ischemia and reperfusion, viral infection and chemical insults are common pathogenic factors of liver-related diseases that usually cause tissue damage and cell death, providing numerous danger signals for the activation of NLRP3 inflammasome. Currently, natural products have attracted much attention as potential agents for the prevention and treatment of liver diseases due to their multitargets and nontoxic natures. A great number of natural products have been shown to exhibit beneficial effects on liver injury induced by various chemicals through regulating NLRP3 inflammasome pathways. In this review, the roles of the NLRP3 inflammasome in chemical-induced liver injury (CILI) and natural products that exhibit beneficial effects in CILI through the regulation of inflammasomes were systematically summarized.
在过去几十年中，人们对无菌性炎症过程的理解取得了重大进展，该过程依赖于一种称为含pyrin结构域3的核苷酸结合寡聚化结构域（NOD）样受体（NLRP3）炎性小体的胞质复合物。NLRP3炎性小体的激活需要两个步骤，包括其配体激活Toll样受体（TLR），导致前细胞因子转录和炎性小体成分激活，以及由各种危险信号触发的NLRP3炎性小体的组装和激活，从而导致半胱天冬酶-1激活，随后半胱天冬酶-1可将前细胞因子切割成其活性形式。代谢紊乱、缺血再灌注、病毒感染和化学损伤是肝脏相关疾病的常见致病因素，通常会导致组织损伤和细胞死亡，为NLRP3炎性小体的激活提供了大量危险信号。目前，天然产物因其多靶点和无毒的特性，作为预防和治疗肝脏疾病的潜在药物受到了广泛关注。大量天然产物已被证明通过调节NLRP3炎性小体途径对各种化学物质诱导的肝损伤具有有益作用。在这篇综述中，系统总结了NLRP3炎性小体在化学诱导的肝损伤（CILI）中的作用以及通过调节炎性小体在CILI中发挥有益作用的天然产物。
