Therapeutic effects of hederacolchiside A1 on particulate matter-induced pulmonary injury

Particulate matter (PM) comprises a hazardous mixture of inorganic and organic particles that carry health risks. Inhaling fine PM particles with a diameter of ≤2.5 μm (PM_2.5) can promote significant lung damage. Hederacolchiside A1 (HA1) exhibits notable in vivo antitumor effects against various solid tumors. However, our understanding of its therapeutic potential for individuals with PM_2.5-induced lung injuries remains limited. Here, we explored the protective properties of HA1 against lung damage caused by PM_2.5 exposure. HA1 was administered to the mice 30 min after intratracheal tail vein injection 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, inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were assessed in mice exposed to PM_2.5. Our data showed that HA1 mitigated lung damage, reduced the W/D weight ratio, and suppressed hyperpermeability caused by PM_2.5 exposure. Moreover, HA1 effectively decreased plasma levels of inflammatory cytokines in those exposed to PM_2.5, including tumor necrosis factor-α, interleukin-1β, and nitric oxide, while also lowering the total protein concentration in BALF and successfully alleviating PM_2.5-induced lymphocytosis. Furthermore, HA1 significantly decreased the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response (MyD) 88, and autophagy-related proteins LC3 II and Beclin 1 but increased the protein phosphorylation of the mammalian target of rapamycin (mTOR). The anti-inflammatory characteristics of HA1 highlights its potential as a promising therapeutic agent for mitigating PM_2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.