Abstract
Ultrafine particulate matter with less than 2.5 μm diameter (PM(2.5)) is an air pollutant that causes severe lung damage. Currently, effective treatment and preventive methods for PM(2.5)-induced lung damage are limited. Cirsilineol (CSL) is a small natural compound isolated from Artemisia vestita. In this study, the efficacy of CSL on PM(2.5)-induced lung toxicity was tested, and its mechanism was identified. Lung injury was caused by intratracheal administration of PM(2.5) suspension in animal models. Two days after PM(2.5) pretreatment, CSL was injected via mouse tail vein for two days. The effects of CSL on PM(2.5)-induced lung damage, autophagy, apoptosis, and pulmonary inflammation in a mouse model and their mechanisms were investigated. CSL significantly suppressed histological lung damage and lung wet/dry weight proportion. CSL also significantly reduced PM(2.5)-induced autophagy dysfunction, apoptosis, lymphocyte suppression, and inflammatory cytokine levels in bronchoalveolar fluid (BALF). Furthermore, CSL increased mammalian target of rapamycin (mTOR) phosphorylation and significantly inhibited the expression of Toll-like receptors (TLR) 2 and 4, MyD88, and the autophagy proteins, Beclin1 and LC3II. Thus, CSL exerts protective effects on pulmonary damage by regulating mTOR and TLR2,4-myD88 autophagy pathways. Therefore, CSL can be used as an effective treatment for PM(2.5)-induced lung damage.