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) 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-induced lung injuries remains limited. Here, we explored the protective properties of HA1 against lung damage caused by PM exposure. HA1 was administered to the mice 30 min after intratracheal tail vein injection of PM. 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. Our data showed that HA1 mitigated lung damage, reduced the W/D weight ratio, and suppressed hyperpermeability caused by PM exposure. Moreover, HA1 effectively decreased plasma levels of inflammatory cytokines in those exposed to PM, including tumor necrosis factor-α, interleukin-1β, and nitric oxide, while also lowering the total protein concentration in BALF and successfully alleviating PM-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-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.