Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Toluene methylation with syngas to para‐xylene by bifunctional ZnZrO_(x)‐HZSM‐5 catalysts

Toluene methylation with methanol on H‐ZSM‐5(Z5)zeolite for the directional transformation of toluene to xylene has been industrialized.However,great challenges remain because of the high energy barrier of methanol deprotonation to the methoxy group,the side reaction of methanol to olefins,coke formation,and the deactivation of zeolites.Herein,we report the toluene methylation coupled with CO hydrogenation to showcase an enhancement in para‐xylene(PX)selectivity by employing a bifunctional catalyst composed of ZnZrO_(x)(ZZO)and modified Z5.The results showed that a PX selectivity of up to 81.8%in xylene and xylene selectivity of 64.8%in hydrocarbons at 10.3%toluene conversion can be realized over the bifunctional catalyst on a fixed‐bed reactor.The selectivity of gaseous hydrocarbons decreased to 10.9%,and approximately half of that was observed in methanol reagent route where the PX selectivity in xylene was 38.8%.We observed that the acid strength,the quantity ratio of Brönsted and Lewis acid sites,and the pore size of zeolites were essential for the PX selectivity.The investigation of the H_(2)/D_(2) kinetic isotope effect revealed that the newborn methyl group in xylene resulted from the hydrogenation of CO rather than toluene disproportionation.Furthermore,the catalyst showed no evident deactivation within the 100 h stability test.The findings offer a promising route for the production of value‐added PX with high selectivity via toluene methylation coupled with syngas conversion.