Wenyang Jieyu Prescription Regulates Hippocampal Neural Plasticity in Depressed Mice via NLRP3/Caspase-1/IL-1β Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effects of Wenyang Jieyu prescription （WJP） on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice， the modeled mice were randomized into model， Wenyang prescription （5.85 g·kg-1）， Jieyu prescription （12.03 g·kg-1）， WJP （16.71 g·kg-1）， and fluoxetine （2.6 mg·kg-1） groups on the weaning day （PD21）， with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then carried out to evaluate the depression state， memory， and learning ability of the mice. Immunohistochemistry （IHC） was employed to observe the ionized calcium-binding adapter molecule-1 （Iba-1） in hippocampal microglia. High performance liquid chromatography （HPLC） was employed to measure the content of noradrenaline （NE） and epinephrine （E） in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the content of interleukin （IL）-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteine aspartate-specific protease-1 （Caspase-1）， IL-1β， synaptophysin （Syn）， and postsynaptic density 95 （PSD95）. ResultCompared with control group， the model group showed decreased sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. The microglia in the model group presented amoeba-like appearance， the Iba1 increased. Moreover， the model group showed decreased content of NE and E （P<0.01）， elevated levels of IL-1β and IL-18 （P<0.01）， down-regulated protein levels of PSD95 and Syn （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. Compared with model group， WJP and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. They recovered the microglia and the Iba1 decreased. Moreover， the drugs increased the content of NE and E （P<0.05， P<0.01）， lowered the levels of IL-1β and IL-18 （P<0.01）， up-regulated the protein levels of PSD95 and Syn （P<0.01）， down-regulated the protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice， with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.

Role of NLRP3 Inflammasome in IgA Nephropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

IgA nephropathy is recognized as the most common primary glomerular disease， with up to 20%-40% of patients developing end-stage kidney disease within 20 years of onset. The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy， and innate immunity is also involved in the pathogenesis. Nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells， mesangial cells， and podocytes. Activated by external stimuli， NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）. The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1 （Caspase-1）， causing the maturation and release of interleukin-18 （IL-18） and interleukin-1β （IL-1β） involved in inflammation. Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes， mesangial cells， endothelial cells， and renal tubular epithelial cells. Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules， exerting therapeutic effects on IgA nephropathy. This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes， aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.

Interaction between NOD-like receptor protein 3 inflammatory corpuscles and mitochondrial dysfunction in the pathogenesis of septic cardiomyopathy / 中华危重病急救医学

Septic cardiomyopathy (SCM) has a high incidence and complex pathogenesis, which can significantly increase the mortality of sepsis patients. NOD-like receptor protein 3 (NLRP3) inflammatory corpuscles play an important role in the pathogenesis of SCM. Mitochondrial dysfunction in cardiomyocytes is also one of the important pathogenesis of SCM. Activation of NLRP3 inflammatory corpuscles is closely related to mitochondrial dysfunction. The study of interaction mechanism between the two is helpful to find a new therapeutic scheme for SCM. This article reviews the interaction between NLRP3 inflammatory corpuscles and mitochondrial dysfunction in the pathogenesis of SCM, as well as the related mechanisms of traditional Chinese medicine (TCM) prevention and treatment of SCM, providing theoretical reference for further exploring therapeutic targets for SCM.

Effect of Nobiletin on LPS-Induced Inflammatory Injury of Mesangium Cells by Regulating AMPK/NLRP3 Signaling Pathway / 中药新药与临床药理

Objective To investigate the effect of nobiletin(Nb)on lipopolysaccharide(LPS)-induced inflammatory injury of mesangium cells(HBZY-1)by regulating AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods HBZY-1 cells were separated into 5 groups:normal control(NC)group,LPS group(100 ng·mL-1 LPS),and Nb group(100 ng·mL-1 LPS+40 μmol·L-1 Nb),Rapamycin(Rap,AMPK/NLRP3 signaling pathway inhibitor)group[100 ng·mL-1 LPS+0.5 μmol·L-1 Rap],and Nb+Rap group(100 ng·mL-1 LPS+40 μmol·L-1 Nb+0.5 μmol·L-1 Rap).MTT was applied to detect the cytotoxicity and proliferation of HBZY-1 cells.ELISA was applied to detect the contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),catalase(CAT),superoxide dismutase(SOD),and glutathione(GSH)in HBZY-1 cells.Flow cytometry was used to detect cell apoptosis.Western Blot was applied to detect the protein levels of AMPK/NLRP3 signaling pathway.Results Compared with the NC group,the levels of CAT,SOD,GSH,cell OD value,and the level of AMPK protein in the LPS group were significantly reduced(P＜0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly increased(P＜0.05).Compared with the LPS group,the levels of CAT,SOD,GSH,OD value,and the level of AMPK protein in the Nb group were significantly increased(P＜0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly decreased(P＜0.05),while the above indicators in the Rap group showed an opposite trend to the Nb group(P＜0.05).Compared with the Nb group,the above indicators in the Nb+Rap group also showed an opposite trend to the Nb group(P＜0.05).Conclusion Nb may alleviate LPS-induced inflammatory injury to MC cells by up-regulating the AMPK/NLRP3 signaling pathway.But down-regulation of the AMPK/NLRP3 signaling pathway may eliminate the improvement effect of Nb on LPS-induced inflammatory injury in MC cells.

Research progress on the role of NLRP3 inflammasome signaling pathway in the occurrence and development of retinal diseases / 国际眼科杂志(Guoji Yanke Zazhi)

The nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is an inflammatory protein complex, and can participate into the inflammatory response. Upon activation, these inflammasomes can lead to Caspase-1 activation, thereby inducing a cascade of inflammatory factor activation and further cell pyroptosis. Excessive activation of inflammasomes will induce the overexpression of inflammatory factors, persistently triggering immune dysregulation and inflammatory chain reactions, even causing severe damage. The recent studies have confirmed a close association between retinal diseases, such as diabetic retinopathy(DR), retinal ischemia-reperfusion injury(RIRI), and proliferative vitreoretinopathy(PVR)with immune dysregulation and inflammatory responses, which is serving as crucial factors in the progression of retinal diseases. This article reviews the NLRP3 inflammasome signaling pathway and its role in the occurrence and development of retinal diseases, in order to provide new ideas for the pathogenesis and prevention of retinal diseases.

Effect and mechanism of dioscin on renal injury in septic rats / 中国药房

OBJECTIVE To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism. METHODS The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group （0.5% sodium carboxymethyl cellulose solution）， dioscin low-dose， medium-dose and high-dose groups （30， 60， 120 mg/kg） and dexamethasone group （positive control， 10 mg/kg）， with 12 rats per group； another 12 rats were selected as the sham operation group （0.5% sodium carboxymethyl cellulose solution）. After 15 minutes of modeling， rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration， the levels of creatinine （Cr）， blood urea nitrogen （BUN）， neutrophil gelatinase associated lipocalin （NGAL）， kidney injury molecule-1 （KIM- 1）， interleukin 6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） in serum and malondialdehyde （MDA） in renal tissue， superoxide dismutase （SOD） activity and the protein expressions of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NOD-like receptor protein 3 （NLRP3） were detected； renal histomorphology was observed. RESULTS Compared with model group， pathological injury of renal tissue was improved significantly in dioscin low-dose， medium-dose and high-dose groups； the levels of Cr， BUN， NGAL， KIM-1， IL-6， IL-1β and TNF-α in serum， MDA level and protein expression of NLRP3 in renal tissue were decreased significantly （P＜0.05）； SOD activity in renal tissue， protein expressions of Nrf2 and HO-1 were increased significantly （P＜0.05）， in a dose-dependent manner （P＜0.05）. The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group， and there was no statistically significant difference in the levels of the above indicators （P＞0.05）. CONCLUSIONS Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome， and realize the inhibition of inflammatory factors and oxidative stress， so as to protect the kidney injury in sepsis.

Effect and mechanism of dioscin on renal injury in septic rats / 中国药房

OBJECTIVE To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism. METHODS The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group （0.5% sodium carboxymethyl cellulose solution）， dioscin low-dose， medium-dose and high-dose groups （30， 60， 120 mg/kg） and dexamethasone group （positive control， 10 mg/kg）， with 12 rats per group； another 12 rats were selected as the sham operation group （0.5% sodium carboxymethyl cellulose solution）. After 15 minutes of modeling， rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration， the levels of creatinine （Cr）， blood urea nitrogen （BUN）， neutrophil gelatinase associated lipocalin （NGAL）， kidney injury molecule-1 （KIM- 1）， interleukin 6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） in serum and malondialdehyde （MDA） in renal tissue， superoxide dismutase （SOD） activity and the protein expressions of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NOD-like receptor protein 3 （NLRP3） were detected； renal histomorphology was observed. RESULTS Compared with model group， pathological injury of renal tissue was improved significantly in dioscin low-dose， medium-dose and high-dose groups； the levels of Cr， BUN， NGAL， KIM-1， IL-6， IL-1β and TNF-α in serum， MDA level and protein expression of NLRP3 in renal tissue were decreased significantly （P＜0.05）； SOD activity in renal tissue， protein expressions of Nrf2 and HO-1 were increased significantly （P＜0.05）， in a dose-dependent manner （P＜0.05）. The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group， and there was no statistically significant difference in the levels of the above indicators （P＞0.05）. CONCLUSIONS Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome， and realize the inhibition of inflammatory factors and oxidative stress， so as to protect the kidney injury in sepsis.

Jiawei Wendantang Regulates NF-κB/NLRP3 Pathway to Reduce Inflammation in Rat Model of Diabetic Atherosclerosis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Jiawei Wendantang in preventing and treating diabetic atherosclerosis by observing the effect of this prescription on the nuclear factor-κB / NOD-like receptor protein 3（NF-κB/NLRP3） pathway and related inflammatory cytokines in rat model of diabetic atherosclerosis. MethodFifty-four SPF-grade rats were randomized into blank， model， atorvastatin （0.9 mg·kg-1·d-1）， and high-， medium-， low-dose （18.2， 9.1， 4.55 g·kg-1·d-1， respectively） Jiawei Wendantang groups. The rats in other groups except the blank group were modeled for diabetic atherosclerosis by intraperitoneal injection of streptozotocin and feeding with a high-sugar high-fat diet， and those in the blank group were injected with an equal dose of citric acid buffer and fed with a regular diet. The drug administration lasted for 4 weeks， and the blood glucose level in the tail vein was measured every 6 days. After the last administration， the rats were anesthetized for sample collection. Enzyme-linked immunosorbent assay was employed to measure the serum levels of interleukin-18 （IL-18）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1）. Western blot was employed to determine the relative protein levels of NF-κB p65， NLRP3， and ICAM-1 in the abdominal aorta. Real-time quantitative polymerase chain reaction was employed to determine the mRNA levels of NLRP3 and interleukin-1β （IL-1β） in the abdominal aorta. The pathological changes in the thoracic aorta were observed by hematoxylin-eosin staining. ResultCompared with the blank group， the model group showed elevated levels of IL-18， CRP， TNF-α， and ICAM-1 in the serum and blood glucose （P<0.05， P<0.01）， up-regulated protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and up-regulated mRNA levels of NLRP3 and IL-1β （P<0.05）. Compared with model group， Jiawei Wendantang lowered the levels of IL-18， CRP， TNF-α， ICAM-1 and blood glucose （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and down-regulated the mRNA levels of NLRP3 and IL-1β （P<0.05， P<0.01）. Moreover， Jiawei Wendantang alleviated the pathological injuries in the thoracic aorta. ConclusionJiawei Wendantang may modulate the NF-κB/NLRP3 signaling pathway to reduce the release and adhesion of inflammatory cytokines and regulate the blood glucose level to treat diabetic atherosclerosis.

Jiedu Tongluo Tiaogan Prescription Protects Pancreatic β Cell by Targeting NLRP3 Inflammasome via TGR5/cAMP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg-1）， high-dose JTTP group （7.2 g·kg-1）， and metformin group （0.2 g·kg-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

Serum levels of ANGPTL4 and NLRP3 in patients with severe traumatic brain injury and their diagnostic value for secondary massive cerebral infarction / 国际检验医学杂志

Objective To explore the changes of serum angiopoietin-like protein 4(ANGPTL4)and NOD-like receptor protein 3(NLRP3)levels after traumatic brain injury(TBI)and their diagnostic value for sec-ondary massive cerebral infarction.Methods A total of 100 TBI patients admitted to the hospital from Au-gust 2019 to August 2021 were enrolled as the TBI group,meantime,100 healthy people in the hospital were enrolled as the control group.The serum levels of ANGPTL4 and NLRP3 were detected by enzyme-linked im-munosorbent assay(ELISA).The clinical characteristics of TBI patients with and without secondary massive cerebral infarction were compared.Receiver operating characteristic(ROC)curve was applied to analyze the serum levels of ANGPTL4 and NLRP3 on their diagnostic value for TBI patients with secondary massive cere-bral infarction.Multivariate Logistic regression analysis was applied to analyze the factors affecting the occur-rence of secondary massive cerebral infarction in TBI patients.Results The serum ANGPTL4 level in TBI group was lower than that in the control group,and the serum NLRP3 level was higher than that in the con-trol group(P<0.05).There were obvious differences in proportion of brain hernia,proportion of subarach-noid hemorrhage,serum levels of ANGPTL4 and NLRP3 between patients with secondary massive cerebral infarction and patients without secondary massive cerebral infarction(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum ANGPTL4 and NLRP3 in diagnosing secondary massive cere-bral infarction in TBI patients was 0.792 and 0.812 respectively,with sensitivity of 77.80%and 83.30%re-spectively,and specificity of 86.60%and 64.60%respectively.The sensitivity,the specificity and AUC of the combined detection were 83.30%,82.90%and 0.867 respectively.Multivariate Logistic regression analysis showed that serum NLRP3 level was a risk factor for TBI patients with secondary massive cerebral infarction(P<0.05).After treatment,it was found that serum ANGPTL4 level increased and NLRP3 level decreased in TBI patients(P<0.05).Conclusion The serum level of ANGPTL4 in TBI patients decreases,while the level of NLRP3 increases,and the level of ANGPTL4 in the serum of patients with secondary massive cerebral in-farction decreases and the level of NLRP3 increases,both of them are of great significance in the diagnosis of secondary massive cerebral infarction in TBI patients.

Impact of andrographolide on intestinal inflammation in rats with diarrhea type irritable bowel syndrome by regulating the NLRP3/caspase-1 signaling pathway / 中华内分泌外科杂志

Objective:To investigate the impact of andrographolide (AND) on intestinal inflammation in rats with diarrhea type irritable bowel syndrome (IBS-D) and its regulatory mechanism on the NLRP3/caspase-1 signaling pathway.Methods:After the IBS-D rat model was established by low concentration acetic acid combined with restraint stress, the rats were grouped into control group, model group, positive drug group, AND low-dose (AND-L) group, AND medium dose (AND-M) group, and AND high-dose (AND-H) group, with 10 rats in each group. The score of fecal traits and fecal water content of rats in each group were detected; the abdominal withdrawal reflex (AWR) of rats in each group was scored; HE staining was applied to observe the changes of colonic histopathology of rats in each group; enzyme linked immunosorbent assay (ELISA) was applied to detect the levels of tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), and interleukin-18 (IL-18) in the colon tissue of rats in each group; Western blot was applied to detect the expression levels of NLRP3, ASC, and caspase-1 proteins in the colon tissue of rats in each group. Results:The scores of fecal traits of rats in the control group was 2.43±0.19, fecal water content was 31.76±2.81, AWR score was 0.43±0.02, TNF-α was 123.49±12.35, IL-6 was 76.45±6.23, IL-1 β was 195.76±15.14 and IL-18 was 167.31±13.92, the protein expression levels of NLRP3 was 0.96±0.06, ASC was 1.01±0.08, and caspase-1 was 0.94±0.06. The scores of fecal traits in model group was 6.12±0.58, fecal water content was 65.24±4.13, AWR score was 2.42±0.18, which were higher than those in control group ( P<0.05), the TNF- α in model group was 315.73±19.47, IL-6 was 231.97±14.65, IL-1 β was 435.83±28.67, IL-18 was 382.56±26.84, the protein expression levels of NLRP3 was 2.41±0.18, ASC was 2.23±0.15, and caspase-1 was 2.15±0.16, which were higher than those in control group ( P<0.05). The scores of fecal traits in the low, medium, and high dose AND groups were 5.38±0.46, 4.57±0.38, 3.31±0.27, fecal water content were 54.68±3.67, 46.87±3.75, 38.11±3.10, AWR scores were 1.79±0.16, 1.35±0.10, 0.69±0.04, which were higher than those in model group ( P<0.05), the TNF- α in the low, medium, and high dose AND groups were 268.65±17.23, 224.91±16.36, 178.16±14.65, IL-6 were 187.74±14.57, 159.64±11.39, 124.18±8.62, IL-1 β were 369.51±21.96, 314.72±23.64, 263.93±16.82, IL-18 were 334.72±25.17, 280.16±21.43, 235.67±19.32, the protein expression levels of NLRP3 were 1.94±0.15, 1.56±0.12, 1.25±0.09, ASC were 1.89±0.14, 1.61±0.13, 1.28±0.10, and caspase-1 were 1.76±0.14, 1.49±0.11, 1.20±0.09, which were higher than those in model group ( P<0.05) . Conclusion:AND may alleviate intestinal inflammation in IBS-D rats by inhibiting the NLRP3/caspase-1 signaling pathway.

Effects of simethicone on gastrointestinal hormones,intestinal floras and inflammatory process mediated by NLRP3 inflammasome in patients with irritable bowel syndrome / 实用医学杂志

Objective To explore the effects of simethicone on gastrointestinal hormones,intestinal floras and inflammatory process mediated by NOD-like receptor protein 3(NLRP3)inflammasome in patients with irritable bowel syndrome(IBS).Methods A total of 120 patients with IBS admitted to the hospital were prospectively enrolled as the research objects between January 1,2021 and December 31,2022,and they were randomly divided into control group(60 cases)and treatment group(60 cases).The control group was treated with compound eosinophil-Lactobacillus,while treatment group was additionally treated with simethicone.The curative effect after treatment,scores of gastrointestinal symptom rating scale(GSRS),levels of somatostatin(SS),vasoactive intestinal peptide(VIP),NLRP3 inflammasome,interleukin-8(IL-8)and interleukin-1β(IL-1β),counts of intestinal floras before and after treatment,and safety during treatment were compared between the two groups.Results After treatment,total response rate of treatment group was higher than that of control group(91.67% vs.76.67% ,P<0.05).After treatment,GSRS scores in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,levels of SS and VIP in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,counts of eosinophil-Lactobacillus and Bifidobacteria were increased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference in counts of intestinal floras between the two groups(P>0.05).After treatment,levels of NLRP3 inflammasome,IL-8 and IL-1β were decreased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference between the two groups(P>0.05).During treatment,there was no significant difference in side effects between the two groups(P>0.05).Conclusion Simethicone can significantly improve response rate of treatment,improve gastrointestinal symptoms and gastrointestinal hormones in IBS patients,which has no significant effects on intestinal floras and inflammatory process mediated by NLRP3 inflammasome,with good safety.

Effect of Yiqi Tongmai Formula in Intervening in Liver Inflammation and Lipidosis in ApoE-∕- Mice Based on NF-κB/NLRP3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E-∕- （ApoE-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

Mechanism of Dendrobium huoshanense Polysaccharide Against Neuroinflammation in Parkinson's Disease Model： Based on NLRP3 Inflammasome / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Dendrobium huoshanense polysaccharide （DHP） against inflammatory damage of neurons in Parkinson's disease （PD） model. MethodSH-SY5Y cells were randomized into blank group， model group， and DHP group. The survival rate of cells was measured by thiazole blue（MTT） assay， and the levels of lactate dehydrogenase （LDH）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） were measured by colorimetric analysis. BV-2 microglia were classified into blank group， model group， DHP group， and MCC950 group （positive control group）， and enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. The expression of NOD-like receptor protein 3 （NLRP3）， adaptor protein apoptosis-associated dot protein （ASC）， cysteine aspartic protease-1 （Caspase-1）， and IL-1β was measured by Western blot. A total of 50 C57BL/6 mice were randomized into blank group， model group， DHP low-dose （100 mg·kg-1） group， DHP equivalent-dose （350 mg·kg-1） group， and MCC950 group （positive control group）， 10 mice in each group. The motor balance and coordination of C57BL/6 mice were observed by beam walking test， tail suspension test and rotarod test. The levels of Iba-1 and tyrosine hydroxylase （TH） were detected by immunofluorescence staining. The damage of dopaminergic neurons in the substantia nigra was detected by FJB staining. The levels of inflammatory factors such as IL-1β， IL-18， and TNF-α in mouse midbrain tissues were detected by ELISA and the protein levels of NLRP3， ASC， Caspase-1， and IL-1β protein were measured by Western blot. ResultCompared with the blank group， the SH-SY5Y model group showed decreased cell survival， increased levels of LDH， ROS， and MDA （P<0.05）， and decreased levels of SOD （P<0.05）. Compared with the model group， the DHP group demonstrated increased cell survival， decreased levels of LDH， ROS， and MDA （P<0.01）， and increased level of SOD （P<0.01）. Compared with the blank group， BV-2 model group had high levels of IL-1β， IL-18， and TNF-α （P<0.05） and high protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.05）. Compared with the model group， DHP and MCC950 groups demonstrated low levels of IL-1β， IL-18， and TNF-α （P<0.01） and low protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.01）. Compared with the blank group， the C57BL/6 model group displayed long time to pass the balance wood （P<0.05）， short time spent on the rod in the rotarod test （P<0.05）， high levels of IL-1β， IL-18， and TNF-α （P<0.05） and expression of Iba-1 in the midbrain substantia nigra （P<0.05）， low TH expression （P<0.05）， more positive neurons in the FJB staining （P<0.05）， and high expression of NLRP3， Caspase-1， ASC， and IL-1β proteins （P < 0.05）. Compared with the model group， the mice in the DHP and MCC950 groups had short time to pass the balance beam （P<0.01）， long time spent on the rod （P<0.01）， low levels of IL-1β， IL-18， and TNF-α （P<0.01）， low Iba-1 expression in midbrain substantia nigra （P<0.01）， high TH expression （P<0.01）， and small number of positive neurons in the midbrain substantia nigra （P<0.01）. The expression of NLRP3， ASC， and IL-1β proteins was lower in the MCC950 group （P<0.01）， and the expression of NLRP3， ASC， Caspase-1 and IL-1β proteins was lower in the DHP equivalent-dose group （P<0.01） than in the model group. ConclusionDHP has anti-oxidative stress effect. It regulates the expression of NLRP3 inflammasome and inhibits the overactivation of microglia， thereby alleviating the neuroinflammatory injury in PD and exerting the neuroprotective effect.

Alcohol Extract of Angelicae Pubescentis Radix Treats Gouty Arthritis Induced by MSU via NLRP3/ASC/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the efficacy and mechanism of the alcohol extract DH50 of Angelicae Pubescentis Radix in treating gouty arthritis induced by monosodium urate （MSU） crystals in vivo and in vitro. MethodFifty male SD rats were randomly assigned into five groups （n=10）： a normal group， a model group， a dexamethasone （DXMS， 0.07 mg·kg-1） group， and low- （DH50-D， 9 mg·kg-1） and high-dose （DH50-G， 18 mg·kg-1） DH50 groups. The rats in the normal group and model group were administrated with the same amount of pure water. On day 5， the gouty arthritis model was established by injecting MSU into the right ankle joint of rats. The toe volume and joint inflammation index were measured 4， 8， 24， and 48 h after modeling. The pathological changes of the synovial tissue were detected by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， and IL-6 in the synovial tissue. Western blot was employed to measure the protein levels of NOD-like receptor protein 3 （NLRP3）， cysteine-aspartic protease-1 （Caspase-1）， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， IL-1β， and cyclooxygenase-2 （COX-2） in the synovial tissue. Furthermore， the cell inflammation model was established with RAW264.7 cells stimulated with MSU （75 mg·L-1）. The cell experiments were carried out with 6 groups： a normal group， a model group， a positive drug （DXMS， 100 μmol·L-1） group， and low- （DH50-D， 25 mg·L-1）， medium- （DH50-Z， 50 mg·L-1）， and high-dose （DH50-G， 100 mg·L-1） DH50 groups. Methyl thiazolyl tetrazolium （MTT） assay was employed to determine the cell viability， ELISA to determine the content of TNF-α in the supernatant of cell culture， and Western blot to determine the protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2. ResultCompared with the normal group， the rat model group showed increased toe swelling degree and joint inflammatory index （P<0.01）， serious infiltration of the synovium， elevated levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， ASC， IL-1β， and COX-2 （P<0.05， P<0.01）. Compared with the rat model group， low- and high-dose DH50 mitigated the toe swelling degree， decreased the joint inflammatory index， alleviated the inflammatory infiltration， lowered the levels of inflammatory cytokines in the tissue homogenate （P<0.01）， and down-regulated the expression of related proteins （P<0.05， P<0.01）. Compared with the normal group， the cell model group showed elevated level of TNF-α in the supernatant （P<0.01） and up-regulated protein levels of NLRP3， cleaved Caspase-1， IL-1β， TNF-α， and COX-2 （P<0.05）. Compared with the model group， low， medium， and high doses of DH50 lowered the level of TNF-α in the supernatant of cell culture in a dose-dependent manner and down-regulated the expression of related proteins （P<0.05， P<0.01）. ConclusionDH50 can mitigate gouty arthritis both in vitro and in vivo by inhibiting the activation of NLRP3 inflammasomes and the production of inflammatory cytokines.

Relationship Between NLRP3 Inflammasome and Diabetic Cardiomyopathy and Intervention Effect of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic cardiomyopathy （DCM） is one of the complications of diabetes. It refers to a specific type of idiopathic cardiomyopathy that occurs in individuals with diabetes， distinct from other cardiovascular diseases such as coronary heart disease， valvular heart disease， or congenital heart disease. It has also been identified as one of the leading causes of death in diabetic patients for many years. Research has shown that the pathogenesis of DCM is closely associated with insulin resistance， activation of various inflammatory responses， increased oxidative stress， impaired coronary microcirculation， and accumulation of advanced glycation end products （AGEs）. Among various inflammatory responses， the activation of the NOD-like receptor protein 3 （NLRP3） inflammasome can induce the secretion of a large amount of pro-inflammatory cytokines through the cascade reaction of inflammation， subsequently mediating cellular pyroptosis and promoting myocardial damage. Currently， extensive experimental studies on traditional Chinese medicine （TCM） have been conducted in China and abroad based on the significant role of the NLRP3 inflammasome in the prevention and treatment of DCM. These studies have demonstrated that Chinese medicinal extracts， such as Astragalus polysaccharide and ginsenoside Rb1， single drugs like Coriolus and Cordyceps， and Chinese medicinal formulas like Didangtang and modified Taohe Chengqitang， as well as acupuncture and TCM exercise therapy， can regulate the relevant pathways of the NLRP3 inflammasome to inhibit its assembly or activation， reduce inflammatory responses， inhibit myocardial remodeling in DCM， and improve cardiac function. This article reviewed the relationship between the NLRP3 inflammasome and DCM， as well as the research progress on TCM in exerting anti-inflammatory effects in this field， aiming to provide new insights for the development of therapeutic approaches for DCM.

Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury.@*METHODS@#Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side.@*RESULTS@#Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group.@*CONCLUSION@#Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

Effect of Shao's five-needle therapy pretreatment on airway inflammatory response in asthmatic rats based on ROS/TXNIP/NLRP3 pathway / 中国针灸

OBJECTIVES@#To explore the possible mechanism of Shao's five-needle therapy pretreatment on relieving airway inflammatory response in asthmatic rats.@*METHODS@#Forty SPF-grade SD rats were randomly divided into a blank group, a model group, an acupuncture group, and a medication group, with 10 rats in each group. Except the blank group, asthma model was established by aerosol inhalation of ovalbumin in the other 3 groups. The rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14) and bilateral "Feishu" (BL 13) and "Fengmen" (BL 12), with each session lasting for 20 min. Acupuncture was given before each motivating, once daily for 7 consecutive days. The rats in the medication group were treated with intraperitoneal injection of dexamethasone sodium phosphate solution before each motivating, once daily for 7 days. General situation of the rats was observed in each group; ELISA method was used to detect the levels of inflammatory cytokines interleukin (IL)-1β and IL-18 in serum; immunofluorescence staining method was performed to assess the expression of reactive oxygen species (ROS) in lung tissues; Western blot method was used to measure the protein expression of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in lung tissues.@*RESULTS@#The rats in the blank group exhibited normal behavior, while those in the model group showed signs of respiratory distress, ear scratching, cheek rubbing, and dysphoria. Compared with the model group, the rats in the acupuncture group and the medication group showed stable respiration and relatively agile responses. Compared with those in the blank group, the serum levels of IL-18 and IL-1β were elevated (P<0.01), the expression intensity of ROS was increased, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were increased (P<0.01) in the model group. Compared with those in the model group, the serum levels of IL-18 and IL-1β were reduced (P<0.01), the expression intensity of ROS was lowered, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were reduced (P<0.01) in the acupuncture group and the medication group. Compared with the medication group, the protein expression of ASC in lung tissue was reduced in the acupuncture group (P<0.05).@*CONCLUSIONS@#Pretreatment of Shao's five-needle therapy could alleviate airway inflammatory response in asthmatic rats by reducing ROS levels and decreasing the aggregation and activation of pathway-related proteins in the ROS/TXNIP/NLRP3 pathway, ultimately leading to decreased secretion of IL-1β and IL-18. This mechanism may contribute to the effectiveness of Shao's five-needle therapy in preventing and treating asthma.

Acacetin protects rats from cerebral ischemia-reperfusion injury by regulating TLR4/NLRP3 signaling pathway / 中国中药杂志

This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1β, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1β, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.

Therapeutic Effect and Mechanism of Regulating Inflammasome NLRP3 Signaling Pathway of Lycopi Herba Extract on Chronic Prostatitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Lycopi Herba extract on chronic prostatitis （CNP） and explore the underlying action mechanism via the inflammasome NOD-like receptor protein 3 （NLRP3） pathway. MethodNormal human prostatic stromal cells， namely WPMY-1 were induced by lipopolysaccharide （LPS） of 5 mg·L-1， and the effects of Lycopi Herba extract of 3.125， 6.25， 12.5， 25， 50， and 100 mg·L-1 on interleukin-6 （IL-6） level released by LPS-induced WPMY-1 cells were detected by enzyme-linked immunosorbent assay （ELISA）. The half-maximal inhibitory concentration （IC50） was calculated. The expression of key proteins in the NLRP3 pathway was detected by western blot after Lycopi Herba extract of 50， 75， and 100 mg·L-1 was administered to WPMY-1 cells. The rat model of CNP was established by injecting carrageenan salt solution into the abdominal lobe of the prostate gland. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the prostate gland in rats. The prostate organ index of rats was measured. The level of 5α-dihydrotestosterone （5α-DHT） in serum， as well as the levels of IL-6， tumor necrosis factor-α （TNF-α）， transforming growth factor-β1 （TGF-β1）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， and inducible nitric oxide synthase （iNOS） in prostate tissue were detected by ELISA. The key protein expressions of COX-2， TGF-β1， and NLRP3 pathway in prostate tissue were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the expressions of COX-2， IL-1β， TGF-β1， and TNF-α mRNA in prostate tissue. ResultCompared with the normal group， the level of IL-6 and the protein expression levels of NLRP3， ASC， Caspase-1， and IL-1β of WPMY-1 cells in the model group were increased （P<0.05， P<0.01）. Compared with the model group， Lycopi Herba extract could inhibit the levels of IL-6 （P<0.01） released by LPS-induced WPMY-1 cells， with IC50 of 38.26 mg·L-1. The protein expression levels of NLRP3， ASC， and IL-1β in the low-， medium-， and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. The expression levels of Caspase-1 protein in medium- and high-dose groups of Lycopi Herba extract were significantly down-regulated （P<0.05， P<0.01）. Compared with the sham operation group， the prostate organ index of rats in the model group was significantly increased （P<0.01）， a large number of inflammatory cells were infiltrated in the prostate tissue， and the histopathological score was significantly increased （P<0.05）； the levels of 5α-DHT in serum， the levels of TNF-α， PGE2， IL-6， TGF-β1， NOS2/iNOS， and COX-2 in prostate tissue， and expression levels of COX-2， IL-1β， and TGF-β1 were significantly increased （P<0.05， P<0.01）. The mRNA expression levels of COX-2， TGF-β1， NLRP3， Caspase-1， ASC， and IL-1β in prostate tissue were significantly up-regulated （P<0.05， P<0.01）. Compared with model group， the low and high doses of Lycopi Herba extract could alleviate the pathological changes in prostate tissue induced by carrageenan， significantly reduce the level of 5α-DHT in serum， levels of TNF-α， PGE2， TGF-β1， and iNOS in prostate tissue （P<0.05， P<0.01）， and mRNA expression levels of COX-2， IL-1β， and TGF-β1 （P<0.05， P<0.01）. The protein expression levels of COX-2， Caspase-1， ASC， and NLRP3 in prostate tissue were significantly down-regulated （P<0.05， P<0.01）. The prostate organ index of the low-dose group of Lycopi Herba extract was significantly decreased （P<0.01）. The level of COX-2 in prostate tissue of the high-dose group of Lycopi Herba extract was significantly decreased， and the protein expression levels of TGF-β1 and IL-1β were significantly down-regulated （P<0.05）. ConclusionLycopi Herba extract has an obvious therapeutic effect on CNP and may reduce inflammation by inhibiting the activation of the inflammasome NLRP3 signaling pathway.