Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling

Macrophage-mediated inflammation plays essential roles in multiple-organ injury. Sinensetin (SNS) at least exhibits anti-inflammation, antioxidant, and antitumor properties. However, the underlying mechanism of SNS-targeted macrophage-mediated inflammation remains elusive. In the present study, our results showed that SNS suppressed lipopolysaccharide (LPS)-induced inflammation to ameliorate lung and liver injuries. Mechanistically, SNS significantly inhibited M1-type macrophage polarization and its NLRP3 inflammasome formation to significantly decrease tumor necrosis factor a (TNFa) and IL-6 expression, while increasing IL-10 expression. Moreover, SNS interacted and activated SIRT1 to promote NRF2 and its target gene SOD2 transcription, which subsequently decreased LPS-induced inflammation. SIRT1 knockdown impaired the effects of SNS on the inhibition of macrophage polarization, NLRP3 inflammasome formation, and NRF2/SOD2 signaling. Taken together, our results showed that SNS is a potential and promising natural active ingredient to ameliorate inflammatory injury via activating SIRT1/NRF2/SOD2 signaling.