The pseudobulb of Pleione bulbocodioides has long been a staple folk medicine in Lijiang’s Naxi community. Locals commonly prepare it via alcohol soaking to treat cough, pulmonary ailments and tumors, featuring low toxicity for both children and the elderly. Researchers interviewed 43 Naxi herbal practitioners across 12 towns in Yulong County and documented traditional processing approaches including fresh application, shade drying and honey-alcohol percolation. Over 70% of interviewed herbalists apply the herb in prescriptions for lung tumor treatment.
Combining untargeted metabolomics with LC-MS/MS quantification, the team detected 938 metabolites falling into 12 chemical categories such as lipids, organic acids and phenylpropanoids from its ethanol extracts. Sclareol was identified and quantified as its key bioactive marker. In vitro tests on A549 lung cancer cells verified that the 95% ethanol extract delivered optimal efficacy with an IC₅₀ value of 118 μg/mL, suppressing cancer cell proliferation, migration and invasion in a dose-dependent manner.
Cellular assays unveiled its anti-tumor pathways: the extract arrests A549 cells at the G0/G1 phase, elevates intracellular reactive oxygen species and disrupts mitochondrial membrane potential. It upregulates pro-apoptotic Bax, downregulates anti-apoptotic Bcl-2 and activates Caspase-3 to trigger cancer cell apoptosis, while cutting MMP2 and MMP9 levels to block metastatic spread.
Via network pharmacology, 118 overlapping targets between herbal ingredients and lung cancer pathogenesis were screened, among which 25 core targets including EGFR and AKT1 were pinpointed. KEGG enrichment analysis indicated the herb exerts anti-cancer effects mainly by modulating EGFR inhibitor resistance and PI3K-Akt signaling pathways. Molecular docking confirmed strong binding affinity of sclareol and Physalolactone B toward core target proteins at the molecular level.
Given severe side effects of conventional chemotherapy and surgery for lung cancer, natural botanical medicines have become a hotspot for targeted drug discovery. This study scientifically validates ancient Naxi medicinal wisdom. The research team plans further in vivo pharmacodynamic and safety tests, followed by active monomer purification and pharmaceutical development. The findings facilitate preservation of Naxi ethnic medicinal resources and open new avenues for novel natural anti-lung-cancer agent research.