{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T07:07:32Z","timestamp":1781680052035,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Qiancao comprises five closely related species: <jats:italic>Rubia cordifolia<\/jats:italic> L., <jats:italic>Rubia yunnanensis<\/jats:italic> Diels., <jats:italic>Rubia wallichiana<\/jats:italic> Decne., <jats:italic>Rubia schumanniana<\/jats:italic> Pritz., and <jats:italic>Rubia magna<\/jats:italic> P. G. Xiao. Due to their similar morphological characteristics, alternative species are frequently substituted for <jats:italic>R. cordifolia<\/jats:italic> L. in traditional medicine. However, the latest National Pharmacopoeia of China only exclusively recognizes <jats:italic>R. cordifolia<\/jats:italic> L. as the official medicinal source. The metabolic differences among these species remain poorly characterized, largely owing to the absence of systematic metabolomic studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study employed a metabolomics approach to investigate the five <jats:italic>Rubia<\/jats:italic> species. The selected species were analyzed using an untargeted metabolomic approach based on ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS\/MS). Subsequently, multivariate statistical analysis combined with bioinformatics was applied to identify differential metabolites and elucidate their associated metabolic pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>This metabolomics analysis identified a total of 1,440 metabolites. Comparative analyses revealed significant differences in the metabolic profiles among the five species. Specifically, we detected 237, 217, 448, and 226 differentially accumulated metabolites when comparing <jats:italic>R. cordifolia<\/jats:italic> L. with <jats:italic>R. magna<\/jats:italic> P. G. Xiao, <jats:italic>R. cordifolia<\/jats:italic> L. with <jats:italic>R. schumanniana<\/jats:italic> Pritz., <jats:italic>R. cordifolia<\/jats:italic> L. with <jats:italic>R. yunnanensis<\/jats:italic> Diels., and <jats:italic>R. cordifolia<\/jats:italic> L. with <jats:italic>R. wallichiana<\/jats:italic> Decne., respectively. KEGG pathway analysis demonstrated substantial involvement of these metabolites in three key pathways: amino acid metabolism, riboflavin metabolism, and terpenoid biosynthesis, with particular emphasis on specific metabolites within these pathways. These findings provide a foundation for future research focused on species identification, quality control, biosynthetic pathway investigation, and bioactivity assessment of Qiancao, thereby advancing the understanding of its clinical applications in traditional Chinese medicine.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1541994","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T05:28:46Z","timestamp":1755494926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Qiancao (Rubia spp.) \u2013 a comprehensive metabolomics analysis of the five core species"],"prefix":"10.3389","volume":"16","author":[{"given":"Mingtong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjun","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.3390\/ph16111586","article-title":"Rubia cordifolia L. attenuates diabetic neuropathy by inhibiting apoptosis and oxidative stress in rats","volume":"16","author":"Bana","year":"2023","journal-title":"Pharmaceuticals"},{"key":"B2","doi-asserted-by":"publisher","first-page":"123114","DOI":"10.1016\/j.jchromb.2022.123114","article-title":"Quality analysis of euryales semen from different origins and varieties based on untargeted metabolomics","volume":"1191","author":"Bao","year":"2022","journal-title":"J. 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