A comprehensive analysis of the potential of two closely related species from the genus Codonopsis as supplementary sources for Codonopsis radix based on metabolomics.

Codonopsis Radix (CR) is a widely used canonical medicinal and edible herb. Its official botanical sources, including C. pilosula (CP), C. pilosula var. modesta (CPM), and C. tangshen (CTS), are geographically constrained. This limited distribution has led to the use of local alternatives, such as C. lanceolata (CL) and C. tubulosa (CT). The scientific basis for substituting these alternatives remains unvalidated. In this study, untargeted metabolomics, network pharmacology, and quantitative analysis were integrated to assess metabolic similarity and identify distinctive bioactive components. Our results demonstrated a conserved core metabolome, with over 90% similarity in metabolite types and 18 shared core active compounds, suggesting a common basis for their traditional medicinal use. Notably, CT exhibited the highest polysaccharide content, and CL was significantly enriched in amino acids. This study not only provides metabolic evidence to support the use of CL and CT as qualified potential supplementary resources for CR but also proposes a dual-track strategy: their core metabolic conservation forms a solid foundation for their potential use as substitutes, while their specialized metabolite enrichment opens avenues for developing targeted functional foods and regionally distinct medicinal products.