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

Integrated analysis reveals effects of bioactive ingredients from Limonium Sinense (Girard) Kuntze on hypoxia-inducible factor (HIF) activation
Integrated analysis reveals effects of bioactive ingredients from Limonium Sinense (Girard) Kuntze on hypoxia-inducible factor (HIF) activation
Limonium Sinense (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 Limonium Sinense using an integrated approach. Water extracts from Limonium Sinense (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 Limonium Sinense, highlighting the rich natural resource and therapeutic values of herbal plants.
1664-462X
Zhao, Hualong
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Wang, Siyuan
acd240a7-88a9-49be-b895-6c0b7d95139e
Zhou, Yilu
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Ertay, Ayse
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Williamson, Philip
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Ewing, Robert
022c5b04-da20-4e55-8088-44d0dc9935ae
Tang, Xinhui
658a1229-49e4-496f-bb83-a121c0ff8ee0
Wang, Jialian
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Wang, Yihua
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Zhao, Hualong
3a22bec4-2334-4036-a0c3-2d9c78ab3717
Wang, Siyuan
acd240a7-88a9-49be-b895-6c0b7d95139e
Zhou, Yilu
1878565d-39e6-467d-a027-7320bf4cdaf2
Ertay, Ayse
fdd0c5cb-cfb2-4e25-9343-cdc462035531
Williamson, Philip
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Ewing, Robert
022c5b04-da20-4e55-8088-44d0dc9935ae
Tang, Xinhui
658a1229-49e4-496f-bb83-a121c0ff8ee0
Wang, Jialian
a41779c4-e567-4843-8e15-015b2d847e0a
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e

Zhao, Hualong, Wang, Siyuan, Zhou, Yilu, Ertay, Ayse, Williamson, Philip, Ewing, Robert, Tang, Xinhui, Wang, Jialian and Wang, Yihua (2022) Integrated analysis reveals effects of bioactive ingredients from Limonium Sinense (Girard) Kuntze on hypoxia-inducible factor (HIF) activation. Frontiers in Plant Science, 13, [994036]. (doi:10.3389/fpls.2022.994036).

Record type: Article

Abstract

Limonium Sinense (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 Limonium Sinense using an integrated approach. Water extracts from Limonium Sinense (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 Limonium Sinense, highlighting the rich natural resource and therapeutic values of herbal plants.

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Accepted/In Press date: 4 October 2022
Published date: 27 October 2022
Additional Information: Funding Information: This project was funded in part by Yancheng Teachers’ University and the University of Southampton. YW was supported by the Medical Research Council [grant no: MR/S025480/1] and an Academy of Medical Sciences/the Wellcome Trust Springboard Award [grant no: SBF002\1038]. SW was supported by China Scholarship Council. YZ was supported by an Institute for Life Sciences Ph.D. Studentship. AE was supported by the Wessex Medical Trust. The authors gratefully acknowledge the Imaging and Microscopy Centre at the Biological Sciences (The University of Southampton) for their support and assistance in this work. We would also like to thank Prof Christopher Schofield (The University of Oxford) and Dr. Matthias Baud (The University of Southampton) for helpful discussions and advice. For the purpose of open access, the authors have applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: Copyright © 2022 Zhao, Wang, Zhou, Ertay, Williamson, Ewing, Tang, Wang and Wang.

Identifiers

Local EPrints ID: 471321
URI: http://eprints.soton.ac.uk/id/eprint/471321
ISSN: 1664-462X
PURE UUID: b5f07a50-6550-451a-ade9-0138ee5ba2fe
ORCID for Hualong Zhao: ORCID iD orcid.org/0000-0002-5009-1444
ORCID for Yilu Zhou: ORCID iD orcid.org/0000-0002-4090-099X
ORCID for Philip Williamson: ORCID iD orcid.org/0000-0002-0231-8640
ORCID for Robert Ewing: ORCID iD orcid.org/0000-0001-6510-4001
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

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Date deposited: 03 Nov 2022 17:32
Last modified: 17 Mar 2024 03:57

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Contributors

Author: Hualong Zhao ORCID iD
Author: Siyuan Wang
Author: Yilu Zhou ORCID iD
Author: Ayse Ertay
Author: Robert Ewing ORCID iD
Author: Xinhui Tang
Author: Jialian Wang
Author: Yihua Wang ORCID iD

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