Evaluation Of The Effect Of Callicarpa Arborea Diterpen And Schisandra Chinensis Triterpene Drivatives On Inhibiting The Activation Of Inflammasome

This paper aims to establish a focal pyrotosis model by using inflammatory activator.The effects of the compounds on the pyrotosis of the cells were evaluated by methods such as kit detection and fluorescence staining microscope observation.Western Blot was used to determine the expression levels of NLRP3 inflammasome-associated proteins in cell pellets and supernatants,ASC oligomerization and histone acetylation levels in cells under the action of different inflammasome stimulators.The number of ASC specks in the cell was observed by immunofluorescence experiment.The signal molecules in multiple signal pathways are determined by Western Blot,and the data is analyzed by statistical analysis methods.To explore the effect of Compound 1 in Callicarpa arborea on the activation and pyrotosis of NLRP3 inflammasomes and its mechanism.Explore the effect of triterpenoid derivatives in Schisandra chinensis on the activation of HDAC and NLRP3 inflammasomes.Compound 1 inhibited the release of LDH and IL-1β,and prevented the occurrence of pyrosis without obvious cytotoxicity.Compound 1 inhibited NLRP3 inflammasome activation induced by three kinds of inflammasome activators in J774A.1 cells and BMdm cells in a dose-dependent manner.Compound 1 prevented the formation of ASC spots and the oligomerization of ASC.Compound 1 affected the phosphorylation of IKK in NF-κB signaling pathway,but did not affect autophagy,AMPK and other pathways.The IC₅₀ of compound 19 to HDAC ranged from 1.139μm to 10.558μM.Compound 19had very low cytotoxicity to J774A.1(CC₅₀>20μm).Through a series of cell level experiments,it was proved that Compound 9 could up regulate the histone acetylation level in J774A.1 cells stimulated the expression of caspase-1 and IL-1β.Compound 1 is an effective inhibitor targeting NLRP3 inflammasome,and compound 1 has great potential.Indepth research is expected to become a new anti-inflammatory targeted drug for the treatment of NLRP3 inflammasome-related diseases.It has extremely important research value.Compound 19 has the activity of inhibiting HDAC,can up-regulate the level of histone acetylation in inflammatory cell models,inhibit the activation of NLRP3 inflammasomes,and has extremely low cytotoxicity to J774A.1,enabling it to be developed into anti-inflammatory cells.The potential of anti-inflammatory drugs.It provides new pharmacological insights for the study of low-toxic HDAC inhibitors as anti-inflammatory drugs.