Silicosis caused by inhalation of
silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat
silicosis.
Tetrandrine is the only
drug approved for
silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established
silicosis mouse models to investigate the effectiveness of
tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for
inflammation and
fibrosis. Moreover, using single cell
RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from
silicosis and control mice, our results provide a novel description of the target pathways for
tetrandrine. Specifically, we found that
tetrandrine attenuated
silicosis by inhibiting both the canonical and non-canonical NLRP3
inflammasome pathways in lung macrophages. Taken together, our work showed that
tetrandrine yielded promising results against
silicosis-associated
inflammation and
fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for
silicosis.