Integrated Analysis of HPLC–QTOF–MS/MS GC–MS and Network Pharmacology Reveals the Effective Substance and Pharmacological Mechanism of Platycodonis Radix

Platycodonis Radix is a well-known traditional Chinese medicine (TCM) for the treatment of respiratory disease. However, its mechanism underlying the traditional efficacy remains unclear and warrants further investigation. The present study aims to elucidate the effective substance and molecular mechanisms. HPLC-QTOF-MS/MS and GC-MS were used to identify the chemical compositions; network pharmacology was adopted to predict the effective substance and possible mechanism. Meanwhile, an in vitro experiment was employed to validate the pharmacological mechanisms. In total, 51 nonvolatile and 20 volatile compounds were tentatively characterized in this study. Among them, 16 active ingredients can act on 323 action targets and 162 signaling pathways to relax bronchial smooth muscle and inhibit airway inflammation and remodeling. Especially, four main predicted active compounds, platycodin D (PD), PE, PD3, and deapio platycodin D (DPD), exerted anti-inflammatory effects by reducing the secretion of NO, PGE2, IL-6, and IL-17 in LPS-induced RAW 264.7 cells. Furthermore, platycodin D could inhibit the protein expression of HSP90, TRAF6, phospho-NF-κB p65, and phospho-ERK1/2. This study analyzed the chemical composition of Platycodonis Radix, clarified that the main active ingredients were triterpenoid saponins, and confirmed the IL-17 signaling pathway as its anti-inflammatory mechanism, which laid the foundation for more in-depth mechanistic research and clinical application.