Phaseolorin J Alleviates Cellular Inflammation and Oxidative Stress by Inhibiting NLRP3 Inflammasome Expression via the Nrf2/HO-1 Pathway

Phaseolorin J (TT-55), a chromone compound isolated and purified from the fermentation products of Phomopsis asparagi DHS-48, is an endophytic fungus obtained from mangrove forests. Preliminary experimental studies have revealed its potent antioxidant and anti-inflammatory activities, though its mechanism of action remains unclear. In this study, we aimed to investigate the molecular mechanisms underlying the antioxidant and anti-inflammatory effects of TT-55, following initial evidence of its potency, by employing an LPS-induced RAW264.7 macrophage model in vitro. The results revealed that in the LPS-induced inflammatory model of RAW264.7 cells, the TT-55 dose dependently inhibited the expression of LPS-induced inflammatory cytokines (TNF-α, IL-18, IL-1β, IL-6) and the production of oxidative stress markers (reactive oxygen species, SOD, MDA). Following combined treatment with the Nrf2 pathway inhibitor ML385 and TT-55, the inhibitory effects of TT-55 on inflammatory cytokines and oxidative stress markers were reversed by ML385. Meanwhile, ML385 also attenuated the ability of TT-55 to suppress LPS-induced upregulation of NLRP3 inflammasome-related genes. In conclusion, TT-55 may exert its antioxidant and anti-inflammatory effects by activating the Nrf2/HO-1 signaling pathway and suppressing the upregulation of NLRP3 inflammasome-related genes.