Platycodon grandiflorum: A promising medicinal and food homologous plant for cigarette smoke-induced chronic bronchitis.

Abstract

Ethnopharmacological relevance: Platycodon grandiflorum (PG), a medicinal food homologous plant, has demonstrated efficacy in the treatment of airway diseases. However, the bioactive compounds and mechanisms of PG against chronic bronchitis (CB) remain poorly characterized. This study is the first to combine in vivo/in vitro component analysis, network pharmacology, and experimental validation to identify PG compounds with anti-CB activity.

Aim of the study: This study established an LPS-induced inflammation model in RAW264.7 cells and a cigarette smoke-induced CB rat model. The therapeutic effects of the 70 % ethanol elution fraction of PG (PG-E_70 %) on CB were evaluated through histopathological examination, assessment of oxidative stress markers, and analysis of inflammatory factor expression. Using a multi-faceted strategy integrating in vivo and in vitro component analysis with network pharmacology data mining, we predicted potential bioactive compounds and mechanisms of PG-E_70 % in CB therapy. Subsequently, a cigarette smoke extract (CSE)-induced 16HBE cell injury model was developed to validate the bioactivity of candidate compounds. Potential therapeutic mechanisms were confirmed via western blotting.

Results: PG-E_70 % significantly alleviated pathological lung tissue damage, oxidative stress, and inflammation. Using UPLC-Q-Exactive-Orbitrap-MS, we identified 104 chemical compounds in PG-E_70 % and 40 blood-entry compounds. In combination with network pharmacology, eight potential bioactive compounds were identified: Platycodin D₃ (PD₃), Platycoside E (PE), Platycoside G₁ (PG₁), Platycodin D (PD), Platyconic acid A (Pa-A), Deapio-platycodin D₃ (DeaP-D₃), Polygalacin D₂ (PolyG-D₂), and Polygalacin D (PolyG-D). These compounds significantly reduced oxidative stress and inflammation and exhibited strong binding affinities for TLR4, MyD88, and NF-κB proteins in molecular docking assays. Western blotting confirmed PG-E70 % downregulated expression of these three proteins.

Conclusion: The results indicate that the active compounds of PG in the treatment of CB are PD₃, PE, PG₁, PD, Pa-A, DeaP-D₃, PolyG-D₂, and PolyG-D. PG mitigates the progression of CB inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. This study provides important evidence supporting the use of PG to treat and prevent cigarette smoke-induced CB.