3β,23-Dihydroxy-12-ene-28-ursolic Acid Isolated from Cyclocarya paliurus Alleviates NLRP3 Inflammasome-Mediated Gout via PI3K-AKT-mTOR-Dependent Autophagy

Figure 10

Schematic diagram of the molecular mechanism of compound 2 in treating against gout. LPS could induce upregulation of NLRP3 and pro-IL-1β through the activation of transcriptional factor NF-κB. MSU caused release of reactive oxygen species, resulting in the release of thioredoxin interaction protein (TXNIP) from thioredoxin (TRX) and subsequently to NLRP3 inflammasome activation. Besides, activated caspase-1 promoted IL-1β production by cleaving pro-IL-1β. Compound 2 inhibited the PI3K/AKT/mTOR pathway and induced autophagy activation, which attenuated ROS production and caused the activation of NLRP3 inflammation to be suppressed. In summary, compound 2 alleviated LPS plus MSU-induced gout inflammatory response by inhibiting NLRP3 inflammasome activation via PI3K-AKT-mTOR-dependent autophagy induction.