Intervention of Traditional Chinese and Western Medicine in NLRP3 Inflammasome-mediated Digestive System Diseases： A Review / 中国实验方剂学杂志

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.

Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage / 中国结合医学杂志

OBJECTIVE@#To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).@*METHODS@#Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot.@*RESULTS@#Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01).@*CONCLUSION@#Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.

Nucleotide-binding Oligomerization Domain-like Receptor Family Pyrin Domain Containing 3 Inflammasome in Alzheimer's Disease / 中国医学科学院学报

Alzheimer's disease(AD)is a chronic neurodegenerative disease whose cause remains unclear.The β-amyloid plaques in the brain are one of the major pathological features of AD.However,the drugs targeting extracellular β-amyloid plaques have failed to cure the disease.Innate immunity and neuroinflammation play a role in the pathogenesis and progression of AD.As the macrophages existing in the central nervous system,microglia are related with extracellular β-amyloid deposition,intracellular neurofibrillary tangle formation,and neuron injury.Accumulating evidence demonstrates that the activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3)inflammasome in microglia plays a role in AD,suggesting new therapeutic target for AD in this signaling pathway.This article reviewed the studies about the activation and regulation of NLRP3 inflammasome in the pathogenesis and progression of AD as well as the development of AD therapies targeting this pathway,aiming to provide reference for further studies in this field.

Role of NLRP3 in the development of silicosis pulmonary fibrosis and the effect of its inhibitor MCC950 / 中国职业医学

OBJECTIVE: To investigate the mechanism of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3( NLRP3) inflammasome in the development and progression of silicosis pulmonary fibrosis,and to explore the effect of NLRP3 inhibitor MCC950 on silicosis pulmonary fibrosis. METHODS: The specific pathogen free Wistar male rats were randomly divided into control group,model group and inhibitor group,with 20 rats in each group.The rats in the model group and the inhibitor group were given a 1. 0 m L of free silica suspension at a concentration of 50 g/L by the non-exposure endotracheal intubation method. Rats in the control group were given an equal volume of sterilized 0. 9% sodium chloride solution. Rats in the inhibitor group were given 10 mg/kg body weight of MCC950 once every other day by gavage,while rats in the model group and the control group were given an equal volume of sterilized0. 9% sodium chloride solution. Five rats were randomly sacrificed at 7,14,28,and 56 days after model establishment.The body weight of the rats was weighed,and the degree of pulmonary alveolitis and pulmonary fibrosis was observed. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin( IL)-1β,IL-18 and transforming growth factor-β1( TGF-β1) of lung tissues. Western blotting was used to detect the relative expression of NLRP3 and Caspase-1protein. RESULTS: The body mass of rats increased with increasing observation time( P < 0. 01). The scores of pulmonary fibrosis and the levels of IL-1β,IL-18 and TGF-β1 in lung tissue had statistical significance in the main effect of dust treatment( P < 0. 01),and the order from high to low was model group,inhibitor group and control group( P < 0. 01). At the time points of 7,14,28,and 56 days after model establishment,the score of pulmonary alveolitis and the relative expression of NLRP3 and Caspase-1 protein in lung tissues in the inhibitor group were lower than that of the model group( P < 0. 01),but higher than that of the control group( P < 0. 01). CONCLUSION: The NLRP3/IL-1β/TGF-β1 signaling pathway plays an important role in the development of silicosis pulmonary fibrosis. MCC950 can inhibit the development and progression of pulmonary fibrosis of silicosis by inhibiting the activation of NLRP3 inflammasome.