AUTHOR=Zhao Hualong , Wang Siyuan , Zhou Yilu , Ertay Ayse , Williamson Philip T. F. , Ewing Rob M. , Tang Xinhui , Wang Jialian , Wang Yihua 

TITLE=Integrated analysis reveals effects of bioactive ingredients from Limonium Sinense (Girard) Kuntze on hypoxia-inducible factor (HIF) activation

JOURNAL=Frontiers in Plant Science

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2022.994036

DOI=10.3389/fpls.2022.994036

ISSN=1664-462X

ABSTRACT=<p><italic>Limonium Sinense</italic> (Girard) Kuntze is a traditional Chinese medicinal herb, showing blood replenishment, anti-tumour, anti-hepatitis, and immunomodulation activities amongst others. However, the mechanism of its pharmacological activities remains largely unknown. Here, we investigated the effects of bioactive ingredients from <italic>Limonium Sinense</italic> using an integrated approach. Water extracts from <italic>Limonium Sinense</italic> (LSW) showed a strong growth inhibitory effect on multiple cells in both 2D and 3D cultures. Global transcriptomic profiling and further connectivity map (CMap) analysis identified several similarly acting therapeutic candidates, including Tubulin inhibitors and hypoxia-inducible factor (HIF) modulators. The effect of LSW on the cell cycle was verified with flow cytometry showing a G2/M phase arrest. Integrated analysis suggested a role for gallic acid in mediating HIF activation. Taken together, this study provides novel insights into the bioactive ingredients in <italic>Limonium Sinense</italic>, highlighting the rich natural resource and therapeutic values of herbal plants.</p>