Study on the mechanism of anti-pulmonary fibrosis action of amygdalin based on transcriptomics and metabolomics.

Pulmonary fibrosis (PF) is closely associated with many chronic lung diseases. Amygdalin has antitussive and asthmatic properties and may play a role in intervening in PF. This study was to investigate the effects of amygdalin on bleomycin-induced PF in rats by integrating pharmacodynamics, transcriptomics, and untargeted metabolomics. The experimental findings indicated that the 20 mg/kg amygdalin group exhibited a significant reduction in inflammatory and fibrotic markers, thereby demonstrating the most pronounced anti-PF effect. Following amygdalin treatment, levels of 117 mRNA and 21 metabolites, including linoleic acid, citrulline and sphingosine 1-phosphate, were significantly restored in PF rats. These mRNAs are enriched in pathways such as neuroactive ligand-receptor interactions, phospholipase D signaling, and linoleic acid metabolism, and these metabolites are closely related to linoleic acid metabolism, arginine biosynthesis, and sphingolipid metabolism. Combined transcriptomic and untargeted metabolomic analyses revealed that amygdalin 's mechanism of action is closely linked to five pathways, including neuroactive ligand-receptor interactions, the phospholipase D signaling pathway and linoleic acid metabolism. These pathways may be the key pathways for the anti-PF of amygdalin. Furthermore, 3 key metabolites and 11 key genes in the key pathway may be closely related to the anti-PF mechanism of amygdalin and are key biomarkers. Furthermore, the study revealed that amygdalin has the capacity to modulate the TGF-β1/Smad signaling pathway and the fibrotic protein marker α-SMA, which may contribute to its anti-PF properties.