A “Qualitative–Pharmacological–Correlation–Molecular” Integrated Workflow Reveals HIF-1α–Relevant Anti-Hypoxia Metabolites in Rhodiola Species
Yixuan Li, Changming Zhong, Nan Zhang, Namin Wei, Siyu Li, Wanjun Yang, Huanfei Yang, Fanlin Yang, Feiyu Li, Jing Shang, Mengrui Guo, Shuo Liu, Jiaqi Tan, Wanting Tang, Zhaojuan Guo, Huaqiang Zhai
TL;DR
This study identifies specific compounds in Rhodiola plants that may help combat hypoxia by combining chemical and biological analyses.
Contribution
A novel integrated workflow combining chemical profiling, pharmacological testing, and molecular validation to identify anti-hypoxia metabolites in Rhodiola species.
Findings
14 compounds were consistently associated with anti-hypoxia efficacy through chemometric and correlation analyses.
Six metabolites showed favorable binding to HIF-1α in molecular docking simulations.
All three Rhodiola species increased survival time in a hypoxia mouse model compared to control.
Abstract
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 “qualitative analysis–pharmacological exploration–correlation analysis–molecular validation” workflow to compare Rhodiola crenulata, R. kirilowii, and R. rosea. Ultra-high-performance liquid chromatography–Q 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–discriminant 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 < 0.05), with mean survival times of 48.16 min (RR), 47.07 min (RC), and 44.82 min…
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Taxonomy
TopicsMedicinal Plants and Bioactive Compounds · Cancer, Hypoxia, and Metabolism · High Altitude and Hypoxia