Abstract
Particulate matter (PM) is a mixture comprising both organic and inorganic particles, both of which are hazardous to health. The inhalation of airborne PM with a diameter of ≤2.5 μm (PM(2.5)) can cause considerable lung damage. Cornuside (CN), a natural bisiridoid glucoside derived from the fruit of Cornus officinalis Sieb, exerts protective properties against tissue damage via controlling the immunological response and reducing inflammation. However, information regarding the therapeutic potential of CN in patients with PM(2.5)-induced lung injury is limited. Thus, herein, we examined the protective properties of CN against PM(2.5)-induced lung damage. Mice were categorized into eight groups (n = 10): a mock control group, a CN control group (0.8 mg/kg mouse body weight), four PM(2.5)+CN groups (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight), and a PM(2.5)+CN group (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight). The mice were administered with CN 30 min following intratracheal tail vein injection of PM(2.5). In mice exposed to PM(2.5), different parameters including changes in lung tissue wet/dry (W/D) lung weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were examined. Our findings revealed that CN reduced lung damage, the W/D weight ratio, and hyperpermeability caused by PM(2.5). Moreover, CN reduced the plasma levels of inflammatory cytokines produced because of PM(2.5) exposure, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and nitric oxide, as well as the total protein concentration in the BALF, and successfully attenuated PM(2.5)-associated lymphocytosis. In addition, CN substantially reduced the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1, and increased protein phosphorylation of the mammalian target of rapamycin (mTOR). Thus, the anti-inflammatory property of CN renders it a potential therapeutic agent for treating PM(2.5)-induced lung injury by controlling the TLR4-MyD88 and mTOR-autophagy pathways.