Metabolism and efficacy-oriented screening of Q-markers for platycodon grandiflorum: A comprehensive evaluation framework of inflammation-specific metabolites and pharmacologically active components in chronic pharyngitis treatment.

Platycodonis Radix (Jiegeng, JG), the dried root of Platycodon grandiflorum (Jacq.) A. DC., is a traditional Chinese medicine frequently utilized for respiratory ailments. Due to the complexity of its saponin constituents, the problems related to quality control indicators are yet to be resolved. This research formulates an integrated approach to screen quality markers (Q-markers) for JG in the treatment of chronic pharyngitis (CP). Initially, the anti-inflammatory efficacy of the JG ethanol extract (JGEE) was verified in a CP rat model through histopathology, inflammatory factor assays, and non-targeted metabolomics. Subsequently, metabolic profiling based on UPLC-Q-TOF-MS identified 41 parent compounds (including 36 platycodins) and 57 metabolites in biological specimens (plasma, urine, feces), uncovering remarkable metabolic disparities between the normal and CP states. A quantitative HPLC-ELSD method was developed to evaluate eight major platycodins, meeting the measurability criterion for Q-markers. In vitro screening in RAW264.7 cells identified seven platycodins with significant anti-inflammatory activity. Pharmacokinetic investigations of these active compounds further emphasized that deapio - platycodin E, platycodin E, platycodin D3, and platycodin D demonstrated pathology - dependent pharmacokinetic behavior, corroborating their association with efficacy (effectiveness) and systemic exposure (transmissibility). In summary, this study constructs a comprehensive "efficacy-metabolism-pharmacokinetics" framework and identifies Deapio - platycodin E, Platycodin E, Platycodin D3, and Platycodin D as potential Q - markers for JG in CP treatment, based on specificity, effectiveness, transmissibility, and measurability.