Puerarin protects against myocardial ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via TLR4/Myd88/NF-κB pathway in rats / 药学学报

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

Tricin's inhibitory effects on TLR4/MyD88/NF-κB pathway of alveolar macrophages in asthma mice / 中成药

AIM To observe the inhibitory effects of tricin on the airway inflammation in low concentration LPS induced asthma mice.METHODS The model of asthma mice with airway inflammation was induced by low concentration LPS plus OVA.There were four groups:blank control group,asthma model group,tricin treatment group and dexamethasone (positive drug) treatment group.The levels of inflammatory factors,including NO,TNF-α and IL-1β,in bronchoalveolar lavage fluid (BALF) were detected by ELISA;the pathology of lung tissue was observed by HE staining;the mRNA and protein expressions of TLR4,MyD88 and NF-κB p65 in alveolar macrophages were detected using real-time quantitative PCR (RT-PCR) and Western blot.RESULTS Tricin could significantly decrease the levels of NO,TNF-α and IL-1β in BALF of asthma mice and improve lung inflammation.It could also down-regulate the relative mRNA and protein expressions of TLR4,MyD88 and NF-κB p65.CONCLUSION Tricin has inhibitory effects on airway inflammation in asthma mice,whose mechanism may be related to the intervention of TLR4/MyD88/NF-κB pathway.