Background/Objectives: The Naxi people in Northwest Yunnan of China have used alcohol-soaked Pleione Pseudobulbus, which is the Pseudobulbus of Pleione bulbocodioides Rolfe (PBR), for lung diseases and tumors for a long period of time. This study aims to explore underlying mechanisms of bioactive ingredients in PBR, as well as to underscore the synergy between traditional medicine and modern pharmacological research. Methods: We verified the anti-tumor effects of the PBR extract through in vitro cell experiments, and explored its underlying mechanisms by combining untargeted metabolomics with network pharmacology to predict the related targets. Results: The anti-tumor potential of PBR extracts was systematically evaluated by integrating chemical profiling with in vitro cell-based assays. Untargeted metabolomics tentatively annotated metabolites spanning 12 major chemical classes, several of which have been previously reported to possess anti-tumor activity. To validate these annotations, prioritized candidates were further examined by LC-MS/MS against authentic reference standards at the nanogram scale, which confirmed the presence of sclareol—a naturally occurring diterpene with documented anti-tumor properties—as a constituent of PBR. Consistent with this chemical evidence, the PBR extract exerted multi-faceted anti-tumor effects in A549 lung cancer cells: it significantly suppressed proliferation, migration, and invasion; induced G0/G1-phase cell-cycle arrest; disrupted mitochondrial membrane potential; and modulated the expression of apoptosis-related proteins. Conclusions: By highlighting the pharmacological properties of cultivated PBR, we identified 118 overlapping targets between PBR compounds and lung disease-related targets, and we further selected 25 core lung cancer targets with high topological importance. This study suggests that the primary active compounds of Pleione bulbocodioides (Franch.) Rolfe may exert anti-lung cancer activity, potentially through targeting the EGFR tyrosine kinase inhibitor resistance pathway and the PI3K-Akt signaling pathway. Furthermore, in silico molecular docking suggested that the two major active compounds exhibited favorable predicted binding affinities with four core targets, particularly EGFR and AKT1, providing a basis for further experimental validation. These results support the potential value of Naxi traditional medicine and the need to further research onthese medicinal plants, thereby promoting Chinese herb medicine conservation efforts in the Naxi region.
Huang et al. (Wed,) studied this question.