Mitochondrion-NLRP3 inflammasome activation in macrophages: A novel mechanism of the anti-inflammatory effect of Notopterygium in rheumatoid arthritis treatment

The mechanism by which Notopterygium (NE) regulates the nucleotide-binding, oligomerization domain (NOD)-like receptor family and pyrin domain-containing 3 (NLRP3) inflammasome to treat rheumatoid arthritis (RA) was investigated to reveal the scientific implications of NE in RA treatment.Adjuvant arthritis (AA) rats were replicated. After NE intervention, the anti-inflammatory efficacy of NE in vivo was determined. The mechanism of NE in RA treatment was predicted by network pharmacology, and the key target for further experiments was found through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG). The effect of NE on the NLRP3 inflammasome in AA rats was verified. Furthermore, with the induction of inflammation in RAW264.7 cells by lipopolysaccharide (LPS), several techniques, such as Griess assay, enzyme linked immunosorbent assays, electron microscopy, and fluorescence probe technology, were used to investigate the anti-inflammatory and related mechanisms of NE in RA treatment.NE could inhibit inflammation in AA rats. KEGG results showed that NLRP3 participated in the top three pathways of NE in RA treatment. Through Western blotting and immunofluorescence assays, this study demonstrated that NE can regulate NLRP3, pro-Caspase-1, Caspase-1, and CD11b in the ankle joint of AA rats. NE may significantly reduce the LPS-induced inflammatory response of RAW264.7 cells by alleviating mitochondrial damage, reducing the number of mitochondrial deoxyribonucleic Acid and mitochondrial reactive oxygen species, inhibiting NLRP3 inflammasome activation.The anti-inflammatory and antirheumatic effect of NE may involve regulating NLRP3 inflammasome activation through mitochondria. NLRP3 is probably the key target molecule of NE in the treatment of RA.