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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.

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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）.

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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.

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Evidence suggests that CXC motif chemokines are involved in neuronal injury and inflammatory processes. Bioinformatics analysis by using data from the Gene Expression Omnibus (GEO) database was performed and identified CXC motif chemokine ligands (CXCLs) as associated with diabetic peripheral neuropathy (DPN). The present study focused on CXC motif chemokine ligand 2 (CXCL2), and the role and potential mechanisms of CXCL2 in DPN were investigated. The DPN rat model was generated by streptozotocin (STZ) injection in vivo, and high-glucose (HG)-stimulated Schwann cell RSC96 was considered a cell model of DPN in vitro. Neuropathic symptoms of DPN were explored by neurological tests and histological examinations. DPN rats showed a decreased level of motor nerve conduction velocity (MNCV) along with typical histological changes. CXCL2 expression was significantly increased in STZ-induced DPN rat sciatic nerve and HG-induced RSC96 cells. Functionally, CXCL2 knockdown inhibited cell apoptosis and inflammation activation under diabetic conditions in vitro and in vivo. CXCL2 knockdown increased cell viability in HG-treated RSC96 cells and reduced apoptosis concerning the decreased expression of cleaved Caspase 3/9. In addition, CXCL2 knockdown protected against NOD-like receptor protein 3 (NLRP3) inflammasome activation and reduced levels of pro-inflammatory cytokines, interleukin (IL)-1ß and IL-18. The repressive effects of CXCL2 knockdown on inflammasome activation under HG conditions were significantly abolished by treatment of the NLRP3 activator nigericin. In conclusion, these results indicated that CXCL2 knockdown exhibited amelioration of hyperglycemia-induced DPN by inhibiting cell apoptosis and NLRP3 inflammasome activation, suggesting that targeting CXCL2 might be a potential strategy for DPN treatment.

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As an effective formula of traditional Chinese medicine, Yang-Gan-Jiang-Mei (YGJM) formula exhibited a unique advantage in ameliorating liver injury and hepatic steatosis of non-alcoholic steatohepatitis (NASH). Nevertheless, the related pharmacological mechanism needs to be elucidated. This study aimed to explore the molecular mechanism of YGJM formula on mitophagy mediated by PINK1/parkin signaling pathway and NOD-like receptor protein 3 (NLRP3) inflammasome in NASH. High-fat-diet rats and HepG2 cells induced by free fatty acid were used as NASH models in vivo and in vitro. Liver pathology and serum indicator embodying liver function (aspartate transferase, alanine transferase, triglyceride, and total cholesterol) were applied to evaluate the extent of hepatic damage and lipid accumulation. Besides, transmission electron microscopy, JC-1 and 2',7'-dichlorofluorescein diacetate were utilized to observe hepatic mitochondrial morphology, as well as cellular mitochondrial membrane potential and reactive oxygen species level. Additionally, expression of PINK1/parkin-mediated mitophagy and NLRP3 inflammasome was detected to elucidate the underlying mechanism of YGJM formula by immunohistochemistry, immunofluorescence, RT-PCR (reverse transcription-polymerase chain reaction) and Western blot. The manifestations of pathology and biochemical detection confirmed the efficacy of YGJM formula in relieving hepatic damage and lipid deposition. Simultaneously, YGJM formula could obviously improve mitochondrial function. In addition, YGJM formula exhibited the promotion of PINK1/parkin-mediated mitophagy, which could perturb NLRP3 inflammasome activation, and as a result, the hepatocyte inflammation was also suppressed both in vitro and in vivo. Our preliminary results indicate that YGJM formula can ameliorate NASH mechanistically by interfering with PINK1/parkin-mediated mitophagy and NLRP3 inflammasome to exert anti-inflammation ability and promote mitochondrial function restoration.

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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.

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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.

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Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.

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ObjectiveTo observe the effect of Huanglian Jiedutang on the inflammatory injury in the mouse model of acute gouty arthritis （AGA） and to explore the mechanism of Huanglian Jiedutang in treating AGA. MethodForty male C57BL/6J mice were randomized into blank， model， colchicine （0.83 mg·kg-1）， and Huanglian Jiedutang （5 g·kg-1） groups. The mouse model of AGA was established by injecting monosodium urate （MSU） crystals into the ankle joint. The swelling degree of the right ankle joint of each mouse was measured every day for 7 days， and the pathological changes of the ankle joint were detected by hematoxylin-eosin （HE） staining after 7 days. The other 40 C57BL/6J mice were grouped as above. After 18 hours of modeling， the right ankle joint was collected， and real-time polymerase chain reaction was employed to measure the mRNA levels of interleukin （IL）-1β， tumor necrosis factor （TNF）-α， IL-6， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The expression levels of IL-1β， TNF-α， and IL-6 were measured by the enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of NLRP3 inflammasome， Toll-like receptor 4 （TLR4）， and nuclear factor-κB （NF-κB）. ResultCompared with the blank group， the model group showed swelling right ankle joint （P<0.01）， obvious foreign body granuloma in the ankle joint with inflammatory cell infiltration. After the treatment with Huanglian Jiedutang， the ankle joint swelling was relieved （P<0.05， P<0.01）， and the size of foreign body granuloma was reduced. Compared with the blank group， the model group showed up-regulated mRNA levels of IL-1β， TNF-α， and IL-6 in the ankle joint tissue （P<0.01）， up-regulated mRNA levels of NLRP3 and Caspase-1 in the NLRP3 inflammasome （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05， P<0.01）. Huanglian Jiedutang down-regulated the mRNA levels of IL-1β， TNF-α， IL-6， NLRP3， and Caspase-1 （P<0.05， P<0.01） and the protein levels of IL-1β， TNF-α， IL-6， NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05 or P<0.01）. ConclusionInjecting MSU crystal resulted in local inflammatory injury of the joints in the mouse model of AGA. The treatment with Huanglian Jiedutang may alleviate the inflammatory injury by regulating the NLRP3 inflammasome and TLR4/NF-κB signaling pathway.

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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.

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ObjectiveTo observe the effects of Sinisan on behaviors and NOD-like receptor protein 3 （NLRP3） inflammasomes of depressed rats induced by chronic unpredictable mild stress （CUMS） and further explore the anti-depressant mechanism of Sinisan. MethodFifty male rats were randomly divided into a normal group， a model group， an NLRP3 inhibitor （MCC950） group （10 mg·kg-1）， and low- （2.5 g·kg-1） and high-dose （5 g·kg-1） Sinisan groups， with 10 rats in each group. The depression model was induced by 42 d CUMS in rats except for those in the normal group. Drug intervention was performed on the 22nd day of modeling by gavage in the Sinisan groups and by intraperitoneal injection in the MCC950 group. Except for the MCC950 group， the remaining four groups received 10 mg·kg-1 physiological saline by intraperitoneal injection， while the rats in the model group， the normal group， and the MCC950 group were administered with 3 mL of physiological saline by gavage. Twenty-one days later， the sucrose preference test and open field test were performed. Western blot was used to detect the protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， ionized calcium-binding adapter molecule 1 （Iba1）， and CD68 in the hippocampus of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the hippocampus of rats. Nissl staining and TUNEL were used to assess the pathological changes and apoptosis level in the hippocampal CA1 region of rats， respectively. ResultThe sucrose preference rate and consumption volume in the sucrose preference test， the total distance， the percentage of central movement distance， and the percentage of residence time in the open field test of rats in the model group were lower than those in the normal group （P<0.01）. Compared with the model group， the Sinisan groups and the MCC950 group showed improved depression-like behaviors， apoptosis level in the hippocampal CA1 region， and neuron loss to varying degrees. Sinisan could reduce the levels of IL-1β， IL-18， Bax， Iba1， and CD68 in the hippocampus （P<0.05， P<0.01）， increase the level of Bcl-2 （P<0.05， P<0.01）， and inhibit the protein expression of NLRP3， ASC， and Caspase-1 related to NLRP3 inflammasomes （P<0.05， P<0.01）. ConclusionSinisan can improve the depression-like behaviors and pathological damage of hippocampal neurons in CUMS-induced rats， and the mechanism may be related to the inflammatory response mediated by the NLRP3 inflammasome signaling pathway.

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Objective:To investigate the effect and mechanism of Chaihu Jia Longgu Mulitang （CJLM） on hippocampal NOD-like receptor protein 3 （NLRP3）inflammasome pathway in rats with depression. Method:Sixty male SD rats were randomly divided into a normal group，a model group， a MCC950 （1 mg·kg^-1） group， and high- （13 g·kg^-1）， medium- （6.5 g·kg^-1）， and low-dose （3.25 g·kg^-1） Chaihu Jia Longgu Mulitang groups， with 10 rats in each group．The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group. Rats were treated correspondingly for 21 days by intraperitoneal injection in the MCC950 group and gavage in other groups. The normal group and the model group received an equal volume of normal saline. The depression-like behaviors of rats were observed by sucrose preference test （SPT） and novelty-suppressed feeding test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of interleukin-1<italic>β </italic>（IL-1<italic>β</italic>） and IL-18 in the hippocampus of depressed rats. Western blot was used to detect the protein levels of NLRP3， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， and Caspase-1. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， prolonged novelty-suppressed feeding time （<italic>P</italic><0.01）， enhanced protein expression of NLRP3，ASC， and caspase-1<italic> </italic>（<italic>P</italic><0.05， <italic>P</italic><0.01）， and elevated expression of IL-1<italic>β</italic> and IL-18 （<italic>P</italic><0.01）. Conclusion:CJLM can alleviate depression-like behaviors in CUMS-induced model rats， and the underlying mechanism is related to the inhibition of the NLRP3 inflammasome pathway．

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Pyroptosis， also known as cell inflammatory necrosis， is different from apoptosis， necrosis， and other forms of cell death in morphological characteristics， occurrence， and regulatory mechanism. It is a new type of programmed cell death dependent on Caspase， which has been discovered and confirmed in recent years. Studies have shown that pyroptosis is closely related to the occurrence of liver diseases， and is critical in alcoholic liver disease （ALD）， non-alcoholic fatty liver disease （NAFLD）， liver fibrosis， and liver cancer. Pyroptosis causes inflammatory injury of hepatocytes to promote the occurrence and development of liver diseases by activating Caspase-1， cleaving the effector gasdermin-D （GSDMD）， and releasing pro-inflammatory cytokines， such as interleukin-18 （IL-18） and interleukin-1β （IL-1β） mainly through the classical NOD-like receptor protein 3 （NLRP3） inflammasome pathway. Clinically， Chinese medicine in the treatment of liver diseases has unique efficacy and low side effects. In the intervention on liver diseases， Chinese medicine blocks the pyroptosis signaling pathway to relieve the liver inflammation by inhibiting the assembly and activation of NLRP3 inflammasome multiprotein complex， blunting the activity of Caspase-1 or Caspase-4/Caspase-5/Caspase-11， and inhibiting the cleavage of GSDMD to reduce the release of pro-inflammatory cytokines such as IL-18 and IL-1β. Therefore， in-depth investigation of pyroptosis facilitates unveiling its role in the occurrence， development， and prognosis of liver diseases， and the enhancement or inhibition of pyroptosis may provide a new strategy for the prevention and treatment of liver diseases by Chinese medicine. At present， NLRP3 inflammasome， a key protein in the classic pyroptosis signaling pathway， has become an anti-liver disease target of Chinese medicine. This study briefly summarized the relationship between pyroptosis and liver diseases and reviewed the intervention of monomers， compound prescriptions， effective fractions and extracts of Chinese medicine in recent years to provide important guidance for further exploring the pathogenic mechanism of pyroptosis and the treatment of liver diseases with Chinese medicine.

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Objective:To explore the progression of diabetic macrovascular disease and the effects of Didangtang at different doses on it. Method:Four-week-old male apolipoprotein-E knockout （ApoE^-/-） mice with diabetic macrovascular disease induced by exposure to high-fat diet combined with streptozotocin （STZ） were randomly divided into the model， simvastatin， as well as high-， medium-， and low-dose Didangtang groups. The age-matched ApoE^-/- mice of the same batch only fed with a high-fat diet were classified into the ApoE^-/- （model control） group， and C57BL/6 mice with the same genetic background receiving a regular diet into the normal group. The sampling was conducted at the 8th and 20th weeks of the experiment for observing the pathological characteristics of the aorta and the proportion of plaque area in mice of each group at different time points， followed by the comparison of blood glucose， blood lipid， and oxidized low-density lipoprotein （ox-LDL） levels. The aortic NOD-like receptor protein 3 （NLRP3） and cysteinyl aspartate-specific proteinase-1 （Caspase-1） protein expression was detected by Western blot assay， and the serum interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-18 （IL-18）， interleukin-1<italic>α</italic> （IL-1<italic>α</italic>）， and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） levels by enzyme-linked immunosorbent assay （ELISA）. Result:The comparison with the normal group revealed that the proportions of plaque area in the ApoE^-/- group and the model group were increased （<italic>P</italic><0.01）， while the proportion of plaque area in each administration group was significantly reduced in contrast to that of the model group （<italic>P</italic><0.05）. The aortic NLRP3 and Caspase-1 protein expression levels as well as the serum IL-1<italic>β</italic>， IL-18， IL-1<italic>α</italic>， and TNF-<italic>α </italic>levels in the ApoE^-/- group and the model group were significantly higher than those in the normal group （<italic>P</italic><0.01）. Compared with the model group， each administration group exhibited a significant reduction in aortic NLRP3 and Caspase-1 protein expression and serum IL-1<italic>β</italic>， IL-18， IL-1<italic>α</italic>， and TNF-<italic>α</italic> levels （<italic>P</italic><0.05）， with the strongest inhibitory effect detected in the medium-dose Didangtang group （<italic>P</italic><0.05）. Conclusion:Didangtang directly alleviates diabetic macrovascular disease possibly by down-regulating NLRP3 and Caspase-1 protein expression and easing the inflammatory cascade.

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Breast cancer type 1 sensitive protein (BRCA1) is a well-known tumor suppressor and its role in oxidative stress has been confirmed. The purpose of this study is to evaluate whether paeonol has a protective effect on myocardial hypoxia-reoxygenation (A/R) injury, and to explore H9C2 cells through a mechanism-dependent pathway mediated by BRCA1. H9C2 cells were pretreated with paeonol (10 µM) for 18 h before hypoxia was induced to establish a cell model of myocardial ischemia/reperfusion (I/R) injury. Use commercial kits to detect antioxidant indicators, including relative oxygen content (ROS) levels, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), lactate dehydrogenase (LDH) activity, and creatine kinase (CK-MB) and nuclear factor-kappaB (NF-κB) activity. The cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction method. Real-time fluorescent quantitative PCR was used to detect BRCA1 mRNA and protein levels. The expression levels of BRCA1, NLRP3 and ACS were determined by Western blotting. In addition, the release of interleukin (IL)-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) was also evaluated by an enzyme-linked immunosorbent assay (ELISA) kit. The results showed that paeonol (10 µM) can significantly improve the hypoxic A/R damage of H9C2 cells, and the BRCA1 expression of H9C2 cells pretreated with paeonol was significantly increased before A/R damage was induced. BRCA1 is widely known in breast and ovarian cancer. Our data proves that the down-regulation of BRCA1 participates in the decrease of cell viability and the decrease of CK-MB and LDH activities, and protects cells by inhibiting the production of ROS and the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes and NF-κB. In conclusion, paeonol significantly improved the A/R damage of H9C2 cells induced by hypoxia through the BRCA1/ROS-regulated NLRP3 inflammasome/IL-1ß and NF-κB/TNF-α/IL-6 pathways. It may be a potential drug against myocardial I/R injury.

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With the increased use of nanomaterials and increased exposure of humans to various nanomaterials, the potential health effects of nanomaterials cannot be ignored. The hepatotoxicity of cobalt nanoparticles (Nano-Co) is largely unknown and the underlying mechanisms remain obscure. The purpose of this study was to exam the hepatotoxicity induced by Nano-Co and its potential mechanisms. Our results showed that exposure of human fetal hepatocytes L02 to Nano-Co caused a dose- and a time-dependent cytotoxicity. Besides the generation of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS), exposure to Nano-Co also caused activation of NOD-like receptor protein 3 (NLRP3) inflammasome in hepatocytes. After silencing NLRP3, one component of NLRP3 inflammasome, expression by siRNA strategy, we found that upregulation of NLRP3-related proteins was abolished in hepatocytes exposed to Nano-Co. Using antioxidants to scavenge ROS and mtROS, we demonstrated that Nano-Co-induced mtROS generation was related to Nano-Co-induced NLRP3 inflammasome activation. Our findings demonstrated that Nano-Co exposure may promote intracellular oxidative stress damage, and mtROS may mediate the activation of NLRP3 inflammasome in hepatocytes exposed to Nano-Co, suggesting an important role of ROS/NLRP3 pathway in Nano-Co-induced hepatotoxicity. These results provide scientific insights into the hepatotoxicity of Nano-Co and a basis for the prevention and treatment of Nano-Co-induced cytotoxicity.

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Objective: To observe the effect of modified Erchentang on the expressions of NLRP3 inflammasome genes in peripheral blood mononuclear cells (PBMCs) and the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)and chemokine8 (CXCL8) in lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the molecular mechanism of modified Erchentang against inflammation of COPD. Method: Forty SD rats were randomly divided into normal control group, model group, MCC950 (NLRP3 inhibitor) group and modified Erchentang group. The COPD model of rats was prepared by using cigarette smoke and dripping with lipopolysaccharide (LPS). During the modeling period (from the 1st to the 30th day), the MCC950 group received a single intraperitoneal injection with 60 mg · kg-1 on the first day of the experiment,and the modified Erchentang group was given intragastric administration with 10 g · kg-1, once every 2 days. From the 31st to the 45th day, the MCC950 group was intraperitoneally injected with 3 mg · kg-1, once every 2 days, the modified Erchentang group was given intragastric administration with 10 g · kg-1, twice a day, and the normal group and the model group received normal saline (NS) with 10 g · kg-1, twice a day. The levels of interleukin-1β(IL-1β), interleukin-18(IL-18) and chemokine8 (CXCL8) in rats lung tissue homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of NLRP3, apoptosis-associated speck-like protein (ASC) and cysteinyl aspartate specific proteinase-1 (Caspase-1) mRNA in PBMCs were measured by Real-time fluorescence quantitative PCR (Real-time PCR). Western blot was used to detect the levels of NLRP3, ASC and Caspase-1 proteins in PBMCs. Immunohistochemical(IHC)method was used to detect the expressions of NLRP3, ASC and Caspase-1 proteins in lung tissues. Result: The expressions of NLRP3, ASC and Caspase-1 mRNA and protein were increased significantly (PPPβ and CXCL8 in lung tissue homogenate in model group were significantly higher than those in the control group. However, compared with model group, the levels of IL-18, IL-1β and CXCL8 were decreased significantly (PPConclusion: NLRP3 inflammasome is involved in the inflammatory response in COPD rats. Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be correlated with the reduction of NLRP3, ASC and Caspase-1 gene expressions, and the inhibition of the release of IL-18, IL-1β and CXCL8.