Anti-inflammatory effects of the Ecklonia cava and Hizikia fusiformis formula (EH) in Phorbol 12-Myristate 13-acetate (PMA)-induced A549 cells and a particulate matter (PM)-induced pulmonary injury mouse model

Environmental particulate matter (PM) exposure is a major contributor to chronic airway inflammation, yet long-term use of conventional drugs is limited by side effects. This study investigated the anti-inflammatory effects and molecular mechanisms of a combined extract from Ecklonia cava and Hizikia fusiformis (EH) in Phorbol 12-myristate 13-acetate (PMA)-stimulated human alveolar epithelial cells (A549) and a PM 10 -induced pulmonary injury mouse model. High-performance liquid chromatography (HPLC) identified dieckol and fucosterol as representative marker compounds of the EH. EH significantly reduced COX-2 protein and MUC5AC mRNA expression, and inhibited ERK and p38 MAPK phosphorylation in vitro , without affecting cell viability. Molecular docking analysis revealed strong binding affinity of dieckol to p38 MAPK, forming multiple stabilizing interactions in the ATP-binding site, whereas neither dieckol nor fucosterol displayed stable COX-2 binding poses. In vivo , EH administration ameliorated PM 10 -induced histopathological pulmonary damage, decreased bronchoalveolar lavage fluid (BALF) total cell counts, and suppressed mRNA expression of COX-2, MUC5AC, IL-6 , and TNF-α . These findings suggest that EH exerts multi-target anti-inflammatory activity primarily through p38 MAPK inhibition by dieckol, supporting its potential as a natural therapeutic strategy for airway inflammation associated with environmental pollutants.