{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:07:40Z","timestamp":1772118460887,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Science and Technology Special Project of Xinjiang Uygur Autonomous Region, China","award":["2023A03006-2"],"award-info":[{"award-number":["2023A03006-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rhodiola species are traditionally used to mitigate hypoxia-related symptoms, but comparative evidence on their chemical bases and active constituents is limited. We implemented an integrated \u201cqualitative analysis\u2013pharmacological exploration\u2013correlation analysis\u2013molecular validation\u201d workflow to compare Rhodiola crenulata, R. kirilowii, and R. rosea. Ultra-high-performance liquid chromatography\u2013Q Exactive mass spectrometry (UPLC-QE-MS) profiling identified 175 metabolites across the three species, of which 161 were shared; multivariate analyses (principal component analysis, PCA; partial least squares\u2013discriminant analysis, PLS-DA) revealed 30 differential compounds. In a normobaric hypoxia mouse model using herbal powder solutions, all three species significantly increased survival time versus control (p &lt; 0.05), with mean survival times of 48.16 min (RR), 47.07 min (RC), and 44.82 min (RK) compared with 44.34 min for the positive control. Chemometric correlation (partial least squares regression, PLSR) combined with grey relational analysis (GRA) prioritized 14 compounds consistently associated with anti-hypoxia efficacy; six representative metabolites\u2014epicatechin, 3-O-galloylquinic acid, salidroside, p-coumaric acid-4-O-glucoside, citric acid, and geraniol\u2014were selected for in silico assessment. Molecular docking against hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) yielded favorable binding poses (docking scores &lt; \u22124.0), providing preliminary molecular-level plausibility without claiming mechanistic proof. This multi-level approach clarifies chemical\u2013pharmacological relationships among Rhodiola species and provides prioritized candidate compounds for targeted isolation and mechanistic validation.<\/jats:p>","DOI":"10.3390\/ijms27052203","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:58:03Z","timestamp":1772114283000},"page":"2203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A \u201cQualitative\u2013Pharmacological\u2013Correlation\u2013Molecular\u201d Integrated Workflow Reveals HIF-1\u03b1\u2013Relevant Anti-Hypoxia Metabolites in Rhodiola Species"],"prefix":"10.3390","volume":"27","author":[{"given":"Yixuan","family":"Li","sequence":"first","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namin","family":"Wei","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyu","family":"Li","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanfei","family":"Yang","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanlin","family":"Yang","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Shang","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengrui","family":"Guo","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Tan","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanting","family":"Tang","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaojuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaqiang","family":"Zhai","sequence":"additional","affiliation":[{"name":"Standardization Research Center of Traditional Chinese Medicine Dispensing, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41580-020-0227-y","article-title":"Cellular adaptation to hypoxia through hypoxia inducible factors and beyond","volume":"21","author":"Lee","year":"2020","journal-title":"Nat. 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