Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury

Abstract

Particulate matter (PM) constitutes a hazardous blend of organic and inorganic particles that poses health risks. Inhalation of fine airborne PM with a diameter of ≤ 2.5 μm (PM 2.5 ) can lead to significant lung impairments. (+)-afzelechin (AZC), a natural compound sourced from Bergenia ligulata, boasts a range of attributes, including antioxidant, antimicrobial, anticancer, and cardiovascular effects. However, knowledge about the therapeutic potential of AZC for patients with PM 2.5 -induced lung injuries remains limited. Thus, in this study, we investigated the protective attributes of AZC against lung damage caused by PM 2.5 exposure. AZC was administered to the mice 30 min after intratracheal instillation of PM 2.5 . Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were evaluated in mice exposed to PM 2.5 . Data demonstrated that AZC mitigated lung damage, reduced W/D weight ratio, and curbed hyperpermeability induced by PM 2.5 exposure. Furthermore, AZC effectively lowered plasma levels of inflammatory cytokines produced by PM 2.5 exposure. It reduced the total protein concentration in BALF and successfully alleviated PM 2.5 -induced lymphocytosis. Additionally, AZC substantially diminished the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1. In contrast, it elevated the protein phosphorylation of the mammalian target of rapamycin (mTOR). Consequently, the anti-inflammatory attribute of AZC positions it as a promising therapeutic agent for mitigating PM 2.5 -induced lung injuries by modulating the TLR4–MyD88 and mTOR–autophagy pathways.