Ethnopharmacological relevance: Particulate matter 2.5 (PM2.5) is a dangerous airborne pollutant that has become a global issue due to its detrimental effect on macrophages. Chenopodium formosanum Koidz (Djulis), a native plant from Taiwan well known for its high antioxidant content and is frequently used in ethnomedicine, shows promise as a novel phytomedicine to combat against oxidative stress caused by PM2.5. However, the protective mechanism of Djulis against PM2.5 still remains unclear. Aim of the study: This study aimed to characterize the deleterious effect of emerging PM2.5 contaminants on the alveolar macrophage cell of the respiratory system and explore the underlying mechanisms in the suppression of PM2.5-induced inflammation using the extract of fermented Djulis. Methods and materials: RNA sequencing, immunoblot, and ChIP assay approaches were used to gain insight into the deleterious effect of PM2.5 on the macrophage cell at the transcriptional and translational level; and to elucidate the contribution of fermented Djulis extract (FCS) as the remedy of PM-induced MH-S cell inflammation. UHPLC-ESI-MS/MS and LC-QQQ/MS were used to identify the bioactive compounds potentially contributing to phytomedicinal properties in the water fraction of FCS. Multiple ligands docking analysis was conducted to predict the in-silico interaction of Djulis metabolites and NF-κB. Results: Here, we showed that PM2.5 exposure at 200 ppm accelerated the production of intracellular ROS and phosphorylated NF-κB (p-NFκB), and negatively affecting the alveolar macrophage cell viability. Treating the cells with water-extracted FCS can restore their viability to 76% while simultaneously suppressing the generation of ROS and p-NFκB up to 38%. These ameliorative effects can be attributed to the occurrence of bioactive compounds such as gluconic acid, uridine, pantothenic acid, L-pyroglutamic acid, L-(−)-malic acid, and acetyl-L-carnitine in the water-extracted FCS which potentially dock to the RELA subunit site and consequently inhibit NF-κB activity along with its downstream inflammation signaling cascade. Conclusion: This work demonstrated the hazardous effect of PM2.5 on alveolar macrophage and unveiled the potential of FCS as a therapeutic phytomedicine to alleviate PM-induced inflammation.
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