Isopanepoxydone inhibits oxidative damage in murine alveolar macrophages via NRF2 and NLRP3 inflammasome

Background: Respiratory diseases due to particulate matter are a serious health issue. We sought to investigate the efficacy of isopanepoxydone (ISO) isolated from the Panus rudis as a therapeutic against particulate matter-induced respiratory complications. Materials and Methods: ISO was isolated from a culture broth of Panus rudis using solvent partition, silica gel, and column chromatography, and high-performance liquid chromatography. Its chemical structure was determined spectroscopically. Murine alveolar macrophages (MH-S) were treated with ISO to investigate the inhibition of nitric oxide (NO) while cytotoxicity was investigated via a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of pro-inflammatory mediators, cytokines, and protein expression levels in the oxidative protective and inflammasome pathway were also investigated. Reactive oxygen species in MH-S cells were investigated using 2',7'-dichlorofluorescein diacetate while immunofluorescence was performed to investigate the expression of activated apoptosis-associated speck-like proteins (ASC) containing a caspase recruitment domain in MH-S cells. Results: ISO effectively inhibited CFA-induced NO production with no cytotoxicity on MH-S cells and pro-inflammatory mediators and cytokines were also inhibited (except tumor necrosis factor a and interleukin-6). ISO enhanced the protein expression of nuclear factor erythroid 2-related factor 2, while suppressing proteins in the inflammasome pathway, but did not suppress the expression of nuclear factor-kappa B. ISO also reduced detectable ROS other than preventing the activation of ASC. Conclusion: Pathways of action of ISO in MH-S cells that prevent oxidative damage and suppress the expression of proteins in the inflammasome pathway were investigated. ISO may be developed as a treatment for respiratory inflammation.

Automated summary

This study investigated the therapeutic efficacy of isopanepoxydone (ISO) isolated from Panus rudis against respiratory complications caused by particulate matter. The results showed that ISO effectively inhibited nitric oxide production, pro-inflammatory mediators, and cytokines in murine alveolar macrophages (MH-S cells). ISO also enhanced the expression of nuclear factor erythroid 2-related factor 2 and suppressed proteins in the inflammasome pathway, indicating its potential as a treatment for respiratory inflammation.