Cultivated Fritillaria cirrhosa bulbs shows comparable chemistry and efficacy to wild-type in Chuanbei Pipa Tangjiang: a metabolomics study.

Fritillaria cirrhosa bulbs (FC) are key Chuanbei Pipa Tangjiang (CPT) ingredient for cough-sputum relief. Wild scarcity prompted cultivation of tissue-cultured and regenerated plantlet bulbs (TFC/RFC), yet their chemical profiles and antitussive-expectorant equivalence to wild bulbs (WFC) in CPT remain unclear. This study compares the chemical profiles and antitussive-expectorant equivalence of CPT prepared from TFC, RFC and WFC (TCPT, RCPT, and WCPT). We compared the chemical profiles of these three CPT types by LC-MS, and used rat plasma metabolomics and mouse antitussive-expectorant model to assess mechanisms and antitussive-expectorant equivalence. Results showed that five marker constituents (sipeimine, platycodin D, etc.) were quantitatively identical across TCPT, RCPT, WCPT, yielding chemical-profile similarities of 89.9% (TCPT vs. WCPT) and 91.0% (RCPT vs. WCPT). Metabolomics indicated that WCPT-derived platycodin D, peimisine and 4-hydroxycinnamic acid modulated eight pathways, including glutathione, vitamin B6 and selenoamino acid metabolism; TCPT and RCPT concordantly regulated pyroglutamate, aldosterone, associated pathways, with OPLS-DA metabolic-profile concordances of 93.75% and 100% to WCPT. TCPT, RCPT, WCPT presented 37, 46, 32 unique blood-entering constituents, respectively; their functional targets lay within - 20% to + 25% bioequivalence margin. The antitussive-expectorant model revealed no inter-group differences. Thus, TFC, RFC and WFC exhibit high chemical, mechanistic and therapeutic concordance in CPT, with RFC serving as an optimal bioequivalent substitute for WFC.