Chen Li, Feng Jianwei, Wang Guina, Liu Si
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Phytomedicine. 2025 Jul;142:156728. doi: 10.1016/j.phymed.2025.156728. Epub 2025 Apr 3.
Allergic asthma (AA) is a prevalent chronic respiratory disease characterized by airway hyperresponsiveness (AHR) and chronic inflammation, significantly impairing patients' quality of life.
This study investigates the therapeutic effects of Platycodin D (PLD) on AA and its underlying mechanisms via the EGFR/PI3K/Akt signaling pathway.
In vitro, BEAS-2B cells treated with IL-4 and IL-13 simulated asthma's inflammatory environment. Enzyme-linked immunosorbent assay (ELISA) assessed PLD's modulation of inflammatory factors, while Western blot (WB) analyzed its impact on airway remodeling proteins. Induced pluripotent stem cells (iPSC)-derived airway organoids (AOs) were used to evaluate PLD's effects on airway remodeling, observed through tissue staining and immunofluorescence. In vivo, an OVA-induced asthma mouse model was employed to assess PLD's therapeutic potential via lung function tests, serum biochemical analysis, and histopathology. Network pharmacology and transcriptomics predicted and validated PLD's target pathways.
In vivo experiments demonstrated that PLD significantly alleviated airway inflammation and remodeling in OVA-induced asthmatic mice. Specifically, treatment with 5 mg/kg PLD significantly reduced the number of inflammatory cells recovered from bronchoalveolar lavage fluid (BALF) compared to the model group (p < 0.05). Serum levels of IgE, IL-4, IL-5, IL-13, and IL-17A were markedly decreased following PLD treatment (p < 0.05). PLD also improved lung function by reducing airway resistance (RL) across all tested methacholine concentrations, with significant reductions at 5, 10, and 20 mg/mL doses (p < 0.05). Histological analysis revealed that PLD attenuated pathological changes in lung tissues, including goblet cell hyperplasia and collagen deposition. Western blot analysis confirmed that PLD significantly downregulated the expression of COL1A1 and α-SMA in lung tissues (p < 0.05), suggesting suppression of airway remodeling. In vitro, PLD inhibited the expression of IL-6, IL-8, COL1A1, and α-SMA in human bronchial epithelial (HBE) cells in a dose-dependent manner. Transcriptomic sequencing and RT-qPCR analysis further demonstrated that PLD downregulated key genes involved in the EGFR/PI3K/Akt pathway. Molecular docking showed high binding affinity between PLD and EGFR/PI3K proteins, supporting a potential mechanistic link.
PLD exerts therapeutic effects in allergic asthma by suppressing airway inflammation, improving lung function, and inhibiting airway remodeling. These effects are associated with the inhibition of the EGFR/PI3K/Akt signaling pathway. Our findings suggest that PLD may serve as a promising candidate for the treatment of allergic airway diseases.
