Role of curcumin-mediated inhibition of inflammation in alleviating brain ischemia-reperfusion synaptic injury / 公共卫生与预防医学

Objective To investigate the potential effect and mechanism of curcumin in inhibiting synaptic injury in the cortex of rats with cerebral ischemia-reperfusion. Methods Sprague-Dawley rats were divided into sham-operated group, model group, low-dose curcumin (50 mg/kg) group, and high-dose curcumin (100 mg/kg) group. A model of middle cerebral artery occlusion for 2 hours and reperfusion for 24 hours was constructed, and curcumin was administered. Based on the neurological function score, the effects of curcumin on cerebral infarct volume, synaptic ultrastructure changes, inflammatory cell infiltration, and the expression of NLRP3, Caspase-1, Synapsin1, and CAMKⅡ were observed after the end of the animal treatment. Results The neurological function scores were 0, 3.25±0.43, 2.50±0.50, and 1.50±0.50 for the sham-operated group, model group, low-dose curcumin group, and high-dose curcumin group, respectively. The percentage of cerebral infarct volume was 0, (38.89±2.21)%, (33.48±1.77)%, and (23.69±2.19)%, respectively. Compared with the sham operation group, the model group had severe synaptic ultrastructure damage, extensive inflammatory cell infiltration, significantly increased expression of Caspase-1 and NLRP3 (P < 0.5), and significantly decreased expression of Synapsin1 and CAMKⅡ (P < 0.5). Curcumin treatment significantly inhibited synaptic damage, reduced inflammatory cell infiltration, decreased the expression of Caspase-1 and NLRP3 (P < 0.5), and increased the expression of Synapsin1 and CAMKII (P < 0.5), when compared with the model group. Conclusion Ischemia-reperfusion-mediated synaptic injury in rat brain triggers an inflammatory response in cortical nerve cells, and curcumin alleviates synaptic damage and reduces brain injury by inhibiting inflammatory factor levels.

The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway / 中医杂志

ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

Trans-palmitoleic acid does not modify the inflammasome expression in a rodent model of diet-induced obesity / El ácido trans-palmitoléico no modifica la expresión del inflamasoma en un modelo murino de obesidad inducida por dieta

Abstract Background: Metabolic disorders such as obesity and type 2 diabetes (T2D) coincide with an increased expression of pro-inflammatory factors. The NLRP3 inflammasome is a complex that activates the pro-inflammatory cytokine IL-1β. (NOD-like receptor protein 3). Some nutrients, such as fatty acids, influence inflammatory processes. For example, in clinical studies, higher trans-palmitoyl acid (TP) concentrations coincide with lower adiposity and lower risk of developing T2D. This study aims to evaluate the effect of TP on NLRP3 expression in a rodent model of diet-induced obesity (DIO). Methods: C57BL/6J mice were fed ad libitum with a control or a high-fat diet (HFD), added with or without TP (3 g/kg diet), for 11 weeks. IL-1β was quantified in serum, and NLRP3-related gene expression was explored in epididymal adipose tissue. Results: Despite increased weight gain in both high-fat groups, the high-fat TP group gained less weight than the high-fat group. In addition, NLRP3 and caspase-1 expression was higher in the HFD groups, but no differences were observed between the HFD and the HFD TP groups. Serum IL-1β levels were not different among groups. Conclusions: Diet supplementation with TP prevents weight gain and has a neutral influence over NLRP3 expression and IL-1β concentration in a DIO mice model.

Resumen Introducción: Las alteraciones metabólicas como la obesidad y diabetes tipo 2 (DT2) coinciden con la expresión aumentada de factores proinflamatorios. Un complejo que induce la activación de la citocina proinflamatoria IL-1β es el inflamasoma NLRP3 (NOD-like receptor protein 3). Algunos nutrimentos, como los ácidos grasos, influencian los procesos inflamatorios. Por ejemplo, en estudios clínicos, mayores concentraciones del ácido trans-palmitoléico (TP) coinciden con una menor adiposidad y un menor riesgo de desarrollar DT2. El objetivo de este estudio fue evaluar el efecto del TP sobre la expresión del inflamasoma NLRP3 en un modelo de obesidad inducida por dieta (OID) en roedores. Métodos: Se alimentaron ratones C57BL/6J ad libitum con una dieta control o alta en lípidos (AL), adicionada o no con TP (3 g/kg dieta), durante 11 semanas. Se cuantificó la concentración de IL-1β en elsuero de los animales, y en el tejido adiposo epididimal se midió la expresión de los componentes del inflamasoma. Resultados: A pesar del aumento de peso en ambos grupos de dieta con alto contenido en lípidos, el grupo alto en lípidos TP ganó menos peso que el grupo AL. Por otro lado, la expresión de genes del inflamasoma resultó mayor en los grupos AL, pero no se encontraron diferencias entre los grupos AL y AL TP. Además, no se observaron diferencias en la concentración de IL-1β en suero entre grupos. Conclusiones: La dieta suplementada con TP previno el aumento del peso corporal, pero no modificó la expresión de los componentes del inflamasoma ni la concentración de IL-1β en suero.

Mecanismos y dianas terapéuticas del inflamasoma NLRP3 en la miocardiopatía diabética / NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy

Resumen La cardiomiopatía diabética es una complicación grave de la diabetes causada por estrés oxidativo, inflamación, resistencia a la insulina, fibrosis miocárdica y lipotoxicidad. Se trata de un padecimiento insidioso, complejo y difícil de tratar. El inflamasoma NLRP3 desencadena la maduración y liberación de citoquinas proinflamatorias, participa en procesos fisiopatológicos como la resistencia a la insulina y la fibrosis miocárdica, además de estar estrechamente relacionado con la aparición y progresión de la cardiomiopatía diabética. El desarrollo de inhibidores dirigidos a aspectos específicos de la inflamación sugiere que el inflamasoma NLRP3 puede utilizarse para tratar la cardiomiopatía diabética. Este artículo pretende resumir el mecanismo y las dianas terapéuticas del inflamasoma NLRP3 en la cardiomiopatía diabética, así como aportar nuevas sugerencias para el tratamiento de esta enfermedad.

Abstract Diabetic cardiomyopathy (DCM) is a serious complication of diabetes caused by oxidative stress, inflammation, insulin resistance, myocardial fibrosis, and lipotoxicity; its nature is insidious, complex and difficult to treat. NLRP3 inflammasome triggers the maturation and release of pro-inflammatory cytokines, participates in pathophysiological processes such as insulin resistance and myocardial fibrosis, in addition to being closely related to the development and progression of diabetic cardiomyopathy. The development of inhibitors targeting specific aspects of inflammation suggests that NLRP3 inflammasome can be used to treat diabetic cardiomyopathy. This paper aims to summarize NLRP3 inflammasome mechanism and therapeutic targets in diabetic cardiomyopathy, and to provide new suggestions for the treatment of this disease.

10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation / 中国天然药物

10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1β secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.

Modified Wuhutang Alleviates Airway Inflammation and Down-regulates Expression of Muc5AC， STAT3， NF-κB， and NLRP3 in Lung Tissues of RSV-infected Asthmatic Mice / 中国实验方剂学杂志

ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin （Muc） 5AC， signal transducer and activator of transcription 3 （STAT3）， nuclear factor kappa B （NF-κB）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3） in respiratory syncytial virus （RSV）-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control （CON）， asthma （ovalbumin， OVA）， RSV infection-induced asthma （OVA+RSV）， high-， medium-， and low-dose （4.08， 2.04， 1.02 g·kg-1·d-1， respectively） modified Wuhutang， and dexamethasone （Dxms， 0.1 g·kg-1d-1） groups （n=10）. The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions （1.0 × 106 PFU·mL-1， 50 μL）. Wuhutang was administrated by gavage， and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration， and then the lung tissue was stained by hematoxylin-eosin （HE） and Van Gieson （VG） for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated （p）-STAT3， STAT3， p-NF-κB， NF-κB， and NLRP3. ResultCompared with the CON group， the OVA group presented airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group， modified Wuhutang alleviated the airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition， and the high-dose group had the best performance. Compared with the CON group， the OVA group and the OVA+RSV group showed increased expression level of Muc5AC （P<0.01）. Compared with the OVA+RSV group， modified Wuhutang reduced the expression level of Muc5AC， and the reduction was significant in the high-dose group （P<0.05）. Compared with the high-dose modified Wuhutang group， Dxms lowered the expression level of Muc5AC （P<0.05）. Compared with the CON group， the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.05， P<0.01）. Compared with the OVA+RSV group， modified Wuhutang down-regulated the protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.01）. Compared with the high-dose modified Wuhutang group， the Dxms group showed up-regulated levels of p-STAT3， p-NF-κB proteins （P<0.01）. ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC， p-STAT3， p-NF-κB， and NLRP3 in RSV-infected asthmatic mice， which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.

Mechanism of Buyang Huanwutang in Regulating Macrophage Cell Polarization Based on TLR4/NF-κB/NLRP3 Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Buyang Huanwutang in regulating macrophage polarization based on the Toll-like receptor 4 （TLR4） / nuclear factor-κB （NF-κB） / nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） pathway. MethodRAW264.7 macrophages were intervened with lipopolysaccharide （LPS） of different concentrations （0， 1.25， 2.5， 5， 10， 20， 40， and 80 mg·L-1） for 24 hours. Cell Counting Kit-8 （CCK-8） assay was used to determine the cell viability of RAW264.7 macrophages. The optimal concentration was chosen to establish an in vitro inflammation model induced by LPS. Cells were divided into a blank group （20% blank serum）， a model group （20% blank serum + 10 mg·L-1 LPS）， a model control group （20% FBS + 10 mg·L-1 LPS）， low-， medium-， and high-dose （5%， 10%， and 20%） Buyang Huanwutang-containing serum groups， a high-dose （20%） Buyang Huanwutang combined with NLRP3 inhibitor MCC950 （50 μmol·L-1） group， a high-dose （20%） Buyang Huanwutang combined with reactive oxygen species （ROS） inhibitor NAC （10 μmol·L-1） group， and a high-dose （20%） Buyang Huanwutang combined with NF-κB inhibitor PDTC （10 μmol·L-1） group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α） in RAW264.7 macrophages. Flow cytometry was employed to measure ROS levels in macrophages. Western blot was used to determine the protein expression of M1-type macrophage-related factors inducible nitric oxide synthase （iNOS） and TNF-α， M2-type macrophage-related factors arginase-1 （Arg-1） and interleukin-10 （IL-10）， as well as the proteins in the TLR4/NF-κB/NLRP3 pathway. ResultCCK-8 results indicated that under 10 mg·L-1 LPS stimulation， RAW264.7 macrophages exhibited the highest cell viability （P<0.01）. Compared with the blank group， the model group showed significantly increased levels of IL-1β， IL-18， and TNF-α （P<0.05，P<0.01）， increased ROS expression （P<0.05，P<0.01）， increased protein expression of M1-type macrophage factors iNOS and TNF-α （P<0.01）， decreased protein expression of M2-type macrophage factors Arg-1 and IL-10 （P<0.05，P<0.01）， and upregulated expression levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated inhibitor of NF-κB （p-IκB）/NF-κB inhibitor （IκB）， phosphorylated NF-κB （p-NF-κB） p65/NF-κB p65， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， and pro-Caspase-1 （P<0.05， P<0.01）. Compared with the model group， all Buyang Huanwutang-treated groups and inhibitor groups significantly reduced levels of IL-1β， IL-18， and TNF-α （P<0.01）， suppressed the expression of inflammatory factors in RAW264.7 macrophages， decreased cellular ROS expression levels （P<0.01）， downregulated M1-type macrophages iNOS and TNF-α protein expression （P<0.01）， upregulated M2-type macrophages Arg-1 and IL-10 protein expression （P<0.01）， and lowered protein expression levels of TLR4， MyD88， p-IκB/IκB， p-NF-κB p65/NF-κB p65， NLRP3， ASC， and pro-Caspase-1 （P<0.05， P<0.01）. ConclusionBuyang Huanwutang can improve macrophage inflammation， potentially by reducing macrophage ROS levels， inhibiting RAW264.7 macrophage polarization， and downregulating the protein expression levels of the TLR4/NF-κB/NLRP3 pathway.

Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through A β/Kv2.1/microglial NLRP3/neuronal tau axis / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

Heat-killed Lactobacillus murinus confers neuropro-tection against dopamine neuronal loss by targeting NLRP3 inflammasome / 中国药理学与毒理学杂志

OBJECTIVE In this study,the effects of live Lactobacillus murinus(L.m)and heat-killed L.muri-nus(H-k L.m)on DA neuronal damage in rats and the underlying mechanisms were investigated.METHODS Male SD rats were randomly divided into five groups:vehicle group,L.m/H-k L.m(1×109 cfu)group,6-OHDH group,6-OHDH + L.m/H-k L.m(1×107 cfu)group,and 6-OHDH + L.m/H-k L.m(1×109 cfu)group.Wild-type and NLRP3 knockout mice were divided into three groups:sham(vehicle),6-OHDH,and 6-OHDH + H-k L.m(1×109 cfu).The model was established after five weeks of pre-administration.Motor ability of experimental mice was assessed by rotarod,mine,and stepping experiments;the expression of dopaminergic neuron markers—tyro-sine hydroxylase(TH),microglial cell markers—ionized calnexin 1(IBA-1),and NOD-like receptor family protein 3(NLRP3)in the substantia nigra was detected by immunohistochemistry and immunofluorescence experi-ments.The expression changes of TH,IBA-1,NLRP3,apoptosis-associated microparticle protein(ASC),cas-pase 1,and inflammatory factors such as interleukin-1β(IL-1β),IL-18,and tumor necrosis factor-α(TNF-α)were detected by immunoblotting experiments.RESULTS H-k L.m ameliorated 6-OHDH-induced motor dysfunctions and loss of substantia nigra DA neurons,while no protec-tion was shown in live L.m treatment.At the same time,H-k L.m reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro-inflammatory factors,thus inhibiting the development of neuroinflammation.Fur-thermore,H-k L.m failed to display its original neuropro-tective properties in NLRP3 inflammasome knockout mice.CONCLUSION H-k L.m conferred neuroprotec-tion against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation,these findings provide a promising potential for future applications of L.m,and also beneficial strategy for PD treatment.

Tetrahydroxy stilbene glycoside ameliorates neuroin-flammation for Alzheimer's disease via cGAS-STING / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Cornel iridoid glycoside alleviates microglia-mediated inflammatory response via NLRP3/calpain pathway / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.

Pharmacological inhibition of STING signaling attenu-ates MPTP-induced neuroinflammation and neurode-generation in experimental models of Parkinson's disease / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects of pharmacological inhibition of STING by C-176,a STING selective inhibitor,in experimental model of Parkinson's disease.METHODS The acute and sub-acute mice mod-els of Parkinson's disease(PD)were established by in-traperitoneal injection of 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydrophine(MPTP).The selective STING inhibitor C-176 was administered by intraperitoneal injec-tion.The potential neuroprotective effects of C-176 were evaluated by behavioral test,tyrosine hydroxylase(TH)immunostaining,Nissl staining,Western blotting,qPCR and immunofluorescence.For in vitro study,the effects of C-176 on LPS/MPP+-induced inflammatory responses in BV2 microglial cells were determined by real time RT-PCR and Western blotting analysis.RESULTS Our study revealed that C-176 significantly inhibited STING signaling activation,ameliorated MPTP-induced dopami-nergic neurotoxicity,motor deficit and associated neuroin-flammation.Furthermore,pharmacological inhibition of STING in BV2 microglia treated with LPS/MPP+ exhibited decreased inflammatory responses.More importantly,C176 also reduced NLRP3 inflammasome activation both in vitro and in vivo.CONCLUSION The results of our study suggest that pharmacologic inhibition of STING protects against neuroinflammation that may act at least in part through suppressing NLRP3 inflammasome acti-vation and thus ameliorated dopaminergic neurodegener-ation.STING signaling may holds great promise for the development of new treatment strategy for PD as an effective therapeutic target.

Effects of NLRP3 inflammasome activation on the proliferation, migration and extracellular matrix deposition of pancreatic stellate cells / 中华胰腺病杂志

Objective:To investigate the effects of NOD-like receptor protein 3(NLRP3) inflammasome activation on the proliferation, migration and extracellular matrix desposition of activated pancreatic stellate cells(PSCs).Methods:The rat PSCs were isolated, cultured and identified, and were divided into control group or LPS group based on the pretreatment with LPS (10 μg/ml for 24 hours) or without. The expression of NLRP3 inflammasome associated molecules in PSCs culture medium was detected by ELISA. The PSCs with NLRP3 inhibition were constructed by shRNA carrying lentivirus infection and were divided into LPS+ negative control group and LPS+ lentivirus group based on whether the cells were treated with LPS and infected by lentivirus or not. The alteration in cell proliferation and migration were detected by CCK-8 kit and transwell chamber method. The expression of extracellular matrix α-SMA and collagen in PSCs was detected by immunofluorescence staining and the expression of TGF-β mRNA was analyzed by RT-qPCR.Results:The cytoplasm of PSCs which were cultured for 24 hours was rich in bright annular lipid droplets, and the cells expressed desmin. After 7 days of culture, the cell became larger in size, the lipid droplets basically disappeared, and the cells were activated and expressed α-SMA. The expression of caspase-1, IL-1β and IL-18 in the supernatant of PSCs culture medium in LPS group were significantly higher than those in control group (1.55±0.04 vs 0.65±0.03), (2.02±0.04 vs 1.05±0.05) and (1.70±0.05 vs 0.97±0.03), respectively. After inhibiting by lentivirus infection, the expression of NLRP3 in the lentivirus group (0.25±0.04) was significantly lower than that in negative control group (0.68±0.05). In control group, LPS group, LPS+ negative control group and LPS+ lentivirus group, the A490 values was 0.61±0.02, 1.15±0.06, 0.96±0.05, and 0.56±0.01, respectively; the migrating PSCs number was (64.12±4.58), (121.67±8.02), (111.67±4.67) and (69.67±8.08)/HF, respectively; the relative expression of α-SMA was 0.78±0.05, 4.12±0.04, 3.81±0.06 and 0.88±0.05, respectively; the relative expression of collagen was 0.65±0.03, 3.43±0.02, 2.67±0.02 and 0.48±0.03, respectively; and the expression of TGF-β mRNA was 0.22±0.03, 0.89±0.01, 0.86±0.03 and 0.43±0.02, respectively. The A490 value, the migrating cells number, the expression of α-SMA, collagen and the expression of TGF-β mRNA in LPS group and LPS+ negative control group was significantly higher than those in control group and LPS+ lentivirus group, and all the differences were statistically significant (all P value <0.05). Conclusions:NLRP3 inflammasome activation may accelerate the extracellular matrix deposition and pancreatic fibrogenesis by promoting PSCs proliferation and migration ability via regulating the biological functions.

Inhibition of lead-induced hepatic inflammation by inhibiting neutrophil granule protein in mice / 中国职业医学

Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups： control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.

Mechanism of Yupingfeng San Against Allergic Rhinitis Through ROS/NLRP3/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Yupingfeng San on allergic rhinitis （AR） and its effect on Reactive oxygen species （ROS）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/cysteinyl aspartate specific proteinase-1 （Caspase-1） pathway. MethodSPF mice were randomly divided into control group， model group， loratadine group （0.9 mg·kg-1）， and low， medium， and high dose Yupingfeng San groups （6， 12， 24 mg·kg-1）， with 10 mice in each group. The control group was given routine feeding， and the other groups were intraperitoneally injected with ［ovalbumin（OVA） + Al（OH）₃ + phosphate buffer solution（PBS）］ suspension once every other day for seven consecutive times. After seven days， 10% OVA solution was instilled in the nose， two times each day for seven consecutive days. After successful modeling， each administration group was intraperitoneally injected with different doses of Yupingfeng San Decoction， and the control group and model group were intraperitoneally injected with an equal volume of normal saline. Symptoms of sneezing， scratching， and runny nose were recorded and scored daily. The levels of ovalbumin specific immunoglobulin E （OVA-sIgE）， histamine， eosinophil cationic protein （ECP）， prostaglandin D2 （PGD2）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-4 （IL-4）， and γ interferon （IFN-γ） in nasal lavage solution and serum of mice were detected by enzyme-linked immunosorbent assay （ELISA）. The damage status of the nasal mucosa was observed by hematoxylin-eosin （HE） staining. The number of goblet cells in the nasal mucosa of mice was observed by periodic acid-Schiff （PAS） staining. The expression of NLRP3 protein in the nasal mucosa of mice was detected by immunohistochemistry. Western blot was used to detect the expressions of NLRP3， cleaved Caspase-1， and cleaved gasdermin D （GSDMD） proteins in the nasal mucosa. The test kit was used to detect the changes in ROS in the nasal cavity of mice in each group. ResultCompared with the control group， the nasal symptoms of the model group were significantly aggravated， and the levels of inflammatory factors OVA-sIgE， histamine， ECP， PGD2， IL-1β， IL-18， and IL-4 in serum and nasal lavage solution were increased （P<0.05，P<0.01）. The levels of IFN-γ were decreased （P<0.05，P<0.01）. The histopathological score， goblet cell number， and ROS content were significantly increased （P<0.01）， and the expressions of pyrodeath-related proteins NLRP3， cleaved Caspase-1， and cleaved GSDMD were increased （P<0.01）. Compared with the model group， the nasal symptoms of the loratadine group and Yupingfeng San groups were significantly relieved， and the levels of inflammatory factors OVA-sIgE， histamine， ECP， PGD2， IL-1β， IL-18， and IL-4 in serum and nasal lavage solution were decreased （P<0.05，P<0.01）. The levels of IFN-γ were increased （P<0.05，P<0.01）. The histopathological scores， goblet cell number， and ROS content were significantly decreased （P<0.05，P<0.01）， and the expressions of pyrodeath-related proteins NLRP3， cleaved Caspase-1， and cleaved GSDMD were decreased （P<0.05，P<0.01）. Compared with the loratadine group， the curative effect of the high dose Yupingfeng San group was further increased （P<0.05，P<0.01）. ConclusionYupingfeng San has a therapeutic effect on AR， and its specific effect may be related to the inhibition of ROS/NLRP3/Caspase-1-induced cell pyroptosis.

Inhibition of photoreceptor apoptosis in mice with retinitis pigmentosa through NF-κB/NLRP3 pathway suppression with Lycium barbarum polysaccharide / 数字中医药（英文）

Objective@# To explore whether Lycium barbarum polysaccharide (LBP) can reduce the apoptosis of retinal photoreceptor cells in retinitis pigmentosa (RP) mice by inhibiting nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling pathway. @*Methods@# (i) In vitro experiments, mouse retinal ganglion cells (661W cells) were divided into normal, model, LBP low-dose (LBP-L, 40 mg/L), LBP middle-dose (LBP-M, 80 mg/L), LBP high-dose (LBP-H, 160 mg/L), and positive drug control (NLRP3 inhibitor, 160 mg/L) groups. And the 661W cells were exposed to varying concentrations of H2O2 ranging from 50 to 400 μmol/L to determine the optimal concentration for inducing apoptosis (200 μmol/L). Then the cell viability was assessed using Cell Counting Kit-8 (CCK-8), while the apoptosis rate was detected by flow cytometry; the expression of NLRP3 was detected by immunofluorescence; and the expression of apoptosis markers was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). (ii) In vivo assays were carried out with the use of C57/BL6 and Rd10 mice. The animal experimental groups were divided into normal, model, LBP-L, LBP-M, LBP-H, and NLRP3 inhibitor groups, in which the normal group was C57/BL6 mice and the other groups were Rd10 mice. Ten mice were included in each group, and the corresponding drugs were administered intragastrically for a duration of four weeks. NF-κB/NLRP3 pathway and the expression of apoptosis markers were observed by electroretinogram, histopathological examination, and WB to assess the effects of LBP on retinal photoreceptor cell apoptosis.@*Results@#(i) In vitro experiments, compared with the normal group, the apoptosis rate of 661W cells in model group was significantly increased (P < 0.01), and the expression levels of key proteins of NF-κB/NLRP pathway, such as NLRP3, NF-κB, p-NF-κB, and pro-apoptotic protein caspase-3, were up-regulated (P < 0.01). The rate of Bax/Bcl-2 was increased (P < 0.01), and the concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly increased (P < 0.01). Compared with the model group, high dose of LBP decreased the apoptosis rate of 661W cells (P < 0.01), and down-regulated the expression levelsof the key proteins of NF-κB/NLRP3 pathway, including NF-κB, NLRP3, p-NF-κB, and caspase-3 (P < 0.01). The rate of Bax/Bcl-2 was decreased (P < 0.01), and the concentrations of IL-1β and TNF-α were decreased (P < 0.01). (ii) In vivo experiments, high dose of LBP significantly increased morphological changes in the outer nuclear layer (ONL) thickness of Rd10 mice, as well as functional changes in the amplitudes of the a-wave and b-wave (P < 0.01), which also down-regulated the expression levels of NF-κB (P < 0.05), NLRP3, p-NF-κB, and caspase-3 (P < 0.01), reduced the Bax/Bcl-2 rate (P < 0.01), and decreased the concentrations of IL-1β (P < 0.01) and TNF-α (P < 0.05). @*Conclusion@#LBP could improve both retinal morphology and function, providing protection to photoreceptors from apoptosis through the inhibition of the NF-κB/NLRP3 pathway.

Chinese Medicine Regulates NLRP3 Inflammasomes to Treat Diabetic Nephropathy： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN）， a major cause of chronic kidney disease （CKD）， aggravates the prevalence of end-stage renal disease （ESRD） and threatens human health. The pathogenesis of DN is complex， in which inflammation is a key pathological link in the cascade injury. Therefore， the treatment targeting inflammation helps to delay the progression of DN. NOD-like receptor protein 3 （NLRP3）， a classical proteasome， acts as an inducer of innate immune responses. The activated NLRP3 inflammasomes produce and release inflammatory mediators to trigger pyroptosis and uncontrolled autophagy and mediate the stress signals promoting renal fibrosis， thus participating in the development and progression of DN. The NLRP3 inflammasome as a core site inducing inflammation is widely involved in DN progression and may be a novel target. The active components and compound prescriptions of Chinese medicines are increasingly applied in the prevention and treatment of DN. The latest studies have discovered that Chinese medicines can treat DN by regulating the activation of NLRP3 inflammasomes. Although studies have been conducted to explore the mechanism of Chinese medicines in the treatment of DN via NLRP3 inflammasome， the systematic review remains to be carried out. This paper reviews the relevant publications in recent years and introduces the research progress from the assembly and activation of NLRP3 inflammasomes， the mechanism of NLRP3 inflammasomes in the treatment of DN， and the regulation of NLRP3 inflammasomes by Chinese medicines for the prevention and treatment of DN， aiming to lay a foundation for the relevant studies and provide new targets and strategies for the prevention and treatment of DN.

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.

Derris eriocarpa Extract Treats Gout via TLR4/NF-κB/NLRP3 Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-gout effect and mechanism of Derris eriocarpa extract by network pharmacological analysis combined with in vivo and in vitro experimental verification. MethodThe chemical components and candidate targets of D. eriocarpa were obtained from the database. The key targets and potential active components of D. eriocarpa in the treatment of gout were screened by the protein-protein interaction analysis， and then the Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the key targets. A mouse model of hyperuricemia was established by intraperitoneal injection of hypoxanthine to observe the effect of D. eriocarpa alcohol extract on hyperuricemia. A rat model of gouty inflammation induced by the injection of microcrystalline sodium urate crystals into the foot and plantar was used to observe the effect of D. eriocarpa alcohol extract on gouty inflammation. A xylene-induced acute inflammation model was established to observe the anti-inflammatory effect of D. eriocarpa alcohol extract. The hot plate test and twisting test were performed to observe the pain-relieving effect of D. eriocarpa. The lipopolysaccharide （LPS）-induced RAW264.7 cells were used to study the anti-gout effect and mechanism of D. eriocarpa alcohol extract. ResultA total of 12 key targets and 15 potential active components were obtained from the D. eriocarpa-component-gout target network. The emodin， betulinic acid， and medicarpin endowed D. eriocarpa with anti-hyperuricemia， anti-inflammatory， and pain-relieving effects by acting on Toll-like receptor 4 （TLR4）， NOD-like reception protein 3 （NLRP3）， and nuclear factor （NF）-κB. Compared with the control group， the model groups showed elevated serum uric acid level in mice （P<0.01）， increased swelling degree of rats （P<0.05， P<0.01）， alleviated the auricular swelling of mice （P<0.05）， reduced the twisting times of mice （P<0.05， P<0.01）， and increased the hot plate pain threshold （P<0.05）. Moreover， the model group showed up-regulated mRNA level of TLR4 and protein levels of TLR4， NF-κB， and NLRP3 in cells （P<0.01）， and elevated levels of TLR4 and NF-κB in the cell supernatant （P<0.05， P<0.01）. Compared with the model group， the alcoholic extracts （20， 10， 5 g·kg-1） of D. eriocarpa lowered the serum uric acid level in hyperuricemic mice （P<0.01）， inhibited foot and plantar swelling in rats （P<0.05， P<0.01）， down-regulated the mRNA level of TLR4 and the protein levels of TLR4， NF-κB， NLRP3 in cells， and lowered the levels of TLR4， TNF-α， NF-κB， and IL-6 in cell supernatants （P<0.05， P<0.01）. ConclusionD. eriocarpa alcohol extract may exert the anti-gout， anti-inflammatory， and pain-relieving effects by regulating the TLR4/NF-κB/NLRP3 signaling pathway.

Jiedu Huoxue Prescription Regulates NF-κB/NLRP3/Caspase-1 to Promote Vascular Reendothelialization in Rat Model of Injured Thoracic Aorta / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Jiedu Huoxue prescription in promoting the reendothelialization of injured vessels by regulating the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3）/cysteine-aspartic acid protease （Caspase）-1-mediated pyroptosis. MethodA rat model of injured thoracic aorta was established by balloon injury， and 36 rats were assigned into shame surgery， model， low-， medium-， and high-dose Jiedu Huoxue prescription， and atorvastatin calcium tablet groups. The injured aortic segment was collected 28 days after surgery. Hematoxylin-eosin （HE） staining and Evans blue staining were conducted to reveal the changes of vascular structural morphology and the reendothelialization of blood vessels， respectively. The enzyme-linked immunosorbent assay （ELISA） was employed to determine the levels of tumor necrosis factor-α （TNF-α）， intercellular adhesion molecule-1 （ICAM-1）， interleukin （IL）-1β， and nitric oxide （NO） in the serum. Western blotting was employed to determine the expression of endothelial nitric oxide synthase （eNOS）， NF-κB p65， phospho-NF-κB p65 （p-NF-κB p65）， NLRP3， and Caspase-1 in the vascular tissue. ResultThe model group showed thickened endovascular membrane， proliferation and disarrangement of smooth muscle cells of the artery wall， obvious inflammatory cell infiltration， and narrowed luminal area. Jiedu Huoxue prescription and atorvastatin calcium tablets mitigated the pathological changes of the thoracic aorta in different degrees. After balloon injury， the endothelial coverage rate of the model group decreased significantly， while Jiedu Huoxue prescription and atorvastatin calcium tablets increased the reendothelialization rate （P<0.05）. Compared with the shame surgery group， the model group showed elevated levels of TNF-α， ICAM-1， and IL-1β （P<0.01） and lowered NO level （P<0.01） in the serum. In addition， the model group presented down-regulated protein level of eNOS （P<0.01） and up-regulated phosphorylation of pyroptosis-associated proteins NLPR3， Caspase-1， and NF-κB p65 in the vascular tissue （P<0.05， P<0.01）. Compared with the model group， Jiedu Huoxue prescription and atorvastatin calcium tablets lowered TNF-α， ICAM-1， and IL-1β levels （P<0.05， P<0.01） and elevated the NO level in the serum （P<0.05， P<0.01）. Moreover， the drugs up-regulated the expression of eNOS （P<0.01） and down-regulated the expression of NLRP3， Caspase-1， and NF-κB p65 （P<0.05， P<0.01） in the vascular tissue. ConclusionJiedu Huoxue prescription can promote the reendothelialization and inhibit the intimal hyperplasia of vessels after balloon injury by regulating the NF-κB/NLRP3/Caspase-1 pathway to inhibit pyroptosis and reduce endothelial inflammatory injury.