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Millions of patients are suffering from ischemic stroke, it is urgent to figure out the pathogenesis of cerebral ischemia–reperfusion (I/R) injury in order to find an effective cure. After I/R injury, pro-inflammatory cytokines especially interleukin-1β (IL-1β) upregulates in ischemic brain cells, such as microglia and neuron. To ameliorate the inflammation after cerebral I/R injury, nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome is well-investigated. NLRP3 inflammasomes are complicated protein complexes that are activated by endogenous and exogenous danger signals to participate in the inflammatory response. The assembly and activation of the NLRP3 inflammasome lead to the caspase-1-dependent release of pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18. Furthermore, pyroptosis is a pro-inflammatory cell death that occurs in a dependent manner on NLRP3 inflammasomes after cerebral I/R injury. In this review, we summarized the assembly and activation of NLRP3 inflammasome; moreover, we also concluded the pivotal role of NLRP3 inflammasome and inhibitors, targeting the NLRP3 inflammasome in cerebral I/R injury.

Background: Intracerebral hemorrhage (ICH) is a debilitating and fatal condition with continuously rising incidence globally, without effective treatment available. Zhilong Huoxue Tongyu (ZLHXTY) capsule is a traditional Chinese medicine that is used for ICH treatment in China. However, the evidence based mechanism is not clear.Purpose: To study the protective effects of ZLHXTY capsules against ICH pathogenesis via targetting nuclear factor kappa β (NFкβ) canonical signalling pathway.Methods: C57BL/6 J mice ICH models using autologous blood injection were used to study the effect of ZLHXTY (1.4 g/kg P.O.) after 24 and 72 hrs of ICH induction. The neurological scoring, corner turn test and balance beam with scoring was performed to assess neurological damage. Hematoxylin/eosin and nissl staining was used for histopathological evaluation. Levels of TNFα, NFкB, iNOS, COX2, IL1, IL6 were measured using real time qPCR and western blotting. Protein levels of IKKβ and IкBα were analyzed through western blotting. Immunofluorescence for co-expression of NeuN/TNFα, NeuN/NFкB, Iba1/TNFα, and Iba1/NFкB was also performed.Results: Treatment with ZLHXTY capsules after ICH ameliorated inflammatory brain injury after 24 and 72 h; revealed by neurological scoring, hematoxylin/eosin and nissl staining. The qPCR and western blot analyses demonstrated significant downregulation of TNFα, NFкB, iNOS, COX2, IL1β and IL6. Further, the IKKβ and IкBα revealed significant downregulation and upregulation respectively in western blot. Immunofluorescence also revealed attenuated expression of TNFα and NFкB in neurons and also low expression of Iba1.Conclusion: ZLHXTY capsules elicit its neuroprotective effect by targetting the NFкβ canonical signalling pathway, thereby ameliorating the ICH induced brain injury.

In this study, the chemical constituents of jujube and jujube fermentation broth were compared by chromatography tandem high‐resolution mass spectrometry for the first time. A total of 68 compounds were detected, and six of them were quantified. The results showed that rutin was hydrolyzed and converted into quercetin during the fermentation process. Further, the antioxidant experiments in vitro were carried out, and the IC50 value of the fermentation broth was lower than that of the jujube extract. Twenty‐three potential bioactive components from jujube samples were identified by a target cell‐based screening method, and triterpenic acid compounds exhibited high cell binding property. These results will help to understand the different biological activities of jujube and its fermented products and will benefit the discovery of new functional components.

Zhilong Huoxue Tongyu capsule (ZHTC) is an effective traditional Chinese medicine compound for the treatment of ischemic stroke, which is widely used in clinical ischemic stroke patients. However, it is uncertain whether ZHTC affects ischemic stroke through gut microbiota and serum metabolites. In this study, a rat model of middle cerebral artery occlusion (MCAO) was prepared. By evaluating motor nerve function score, cerebral infarct size, brain tissue damage and intestinal barrier damage, it was found that ZHTC improved stroke-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, fecal microbial transplantation (FMT), untargeted metabolomics, and spearman correlation analysis of gut microbiota and serum metabolites, we found that ZHTC can regulate the abundance of p_Firmicutes, p_Bacteroidota,p_Proteobacteria, g_Prevotella, and g_Lactobacillus, and regulated 23 differential metabolites. Spearman correlation analysis found that Arginine was positively correlated with p_Firmicutes, o_Clostridiales, c_Clostridia, and negatively correlated with p_Bacteroidetes, c_Bacteroidia,o_Bacteroidales; L-Lysine was negatively correlated with f_Christensenellaceae; L-methionine was positively correlated with o_Lactobacillales, f_Lactobacillaceae, and g_Lactobacillus. Altogether, this study shows for the first time that ZHTC can ameliorate ischemic stroke by modulating gut microbiota and metabolic disturbances. This lays the foundation for further revealing the causal relationship between ZHTC, gut dysbiosis, plasma metabolite levels and ischemic stroke, and provides a scientific explanation for the ameliorating effect of ZHTC on ischemic stroke.