BackgroundPulmonary fibrosis (PF) is a chronic progressive disease characterized by inflammatory response and fibroblast activation. This process leads to abnormal deposition of extracellular matrix (ECM). However, the existing clinical treatment methods have significant side effects, poor patient compliance, and limited efficacy. Fritillariae Pallidiflorae Bulbus (BFP) refers to the desiccated bulb of Fritillaria pallidiflora Schrenk, employed for managing persistent pulmonary conditions, with alkaloids as its main active compounds.MethodsThis study examined the efficacy and mechanism of action of the total alkaloids of Fritillariae Pallidiflorae Bulbus (BFP-TA) in treating PF. The material composition of BFP-TA was assessed through High-Performance Liquid Chromatography with Evaporative Light-Scattering Detector (HPLC-ELSD), High-Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (HPLC-Q-TOF-MS/MS). The potential molecular mechanisms of BFP-TA were explored through multi-omics analysis and molecular biology techniques in a rat model of PF induced by bleomycin (BLM). The effects and mechanisms of the medicated plasma components of BFP-TA were validated by integrating blood component analysis with a TGF-β1-induced A549 cell model.ResultsIn BFP-TA, 182 components were detected, comprising 26 alkaloids from genus Fritillariae, with 9 of these alkaloids representing 63.643% of the total. BFP-TA has been shown to improve the progression of PF in rats by reducing inflammation and the PF phenotype. Multi-omics analysis suggests that BFP-TA may alleviate PF by regulating Rap1/ERK signaling pathway. It may also be related to biological processes such as cell migration and cell adhesion. The primary blood-entering component of BFP-TA is imperialine, which exhibits a significant anti-PF effect.ConclusionThis study explored the therapeutic effect of BFP-TA on PF. The results showed that BFP-TA may regulate the Rap1/ERK signaling pathway to reduce the expression of pro-inflammatory factors and collagen deposition, thereby improving lung injury and fibrosis. The imperialine in BFP-TA also contributes to the anti-fibrosis ability.