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Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium
Li, Yi1; Liu, Xiao Tian1; Zhang, Pei Lin1; Li, Yu Chen1; Sun, Meng Ru1; Wang, Yitao2; Wang, Shengpeng2; Yang, Hua1; Liu, Bao Lin1; Wang, Mei3; Gao, Wen1; Li, Ping1
2022-04-01
Source PublicationAntioxidants
ISSN2076-3921
Volume11Issue:4
Abstract

Zonula occludens-1 (ZO-1) is a tight junction protein in the cerebrovascular endothelium, responsible for blood–brain barrier function. Hydroxysafflor yellow A (HSYA) is a major ingredient of safflower (Carthamus tinctorius L.) with antioxidative activity. This study investigated whether HSYA protected ZO-1 by targeting ROS-generating NADPH oxidases (NOXs). HSYA administration reduced cerebral vascular leakage with ZO-1 protection in mice after photothrombotic stroke, largely due to suppression of ROS-associated inflammation. In LPS-stimulated brain microvascular endothelial cells, HSYA increased the ratio of NAD/NADH to restore Sirt1 induction, which bound to Von Hippel–Lindau to promote HIF-1αdegradation. NOX2 was the predominant isoform of NOXs in endothelial cells and HIF-1α transcriptionally upregulated p47phox and Nox2 subunits for the assem-bly of the NOX2 complex, but the signaling cascades were blocked by HSYA via HIF-1α inactivation. When oxidate stress impaired ZO-1 protein, HSYA attenuated carbonyl modification and prevented ZO-1 protein from 20S proteasomal degradation, eventually protecting endothelial integrity. In mi-crovascular ZO-1 deficient mice, we further confirmed that HSYA protected cerebrovascular integrity and attenuated ischemic injury in a manner that was dependent on ZO-1 protection. HSYA blocked HIF-1α/NOX2 signaling cascades to protect ZO-1 stability, suggestive of a potential therapeutic strategy against ischemic brain injury.

KeywordCerebral Microvascular Endothelium Hif-1α Hydroxysafflor Yellow a Nox2 Zo-1
DOI10.3390/antiox11040728
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Food Science & Technology
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal ; Food Science & Technology
WOS IDWOS:000786270400001
Scopus ID2-s2.0-85127651457
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorGao, Wen; Li, Ping
Affiliation1.State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, No. 24 Tongjia Lane, 210009, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao
3.Leiden University-European Center for Chinese Medicine and Natural Compounds, Institute of Biology/SU BioMedicine, Leiden University, Leiden, Sylviusweg 72, 2333 BE, Netherlands
Recommended Citation
GB/T 7714
Li, Yi,Liu, Xiao Tian,Zhang, Pei Lin,et al. Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium[J]. Antioxidants,2022,11(4).
APA Li, Yi,Liu, Xiao Tian,Zhang, Pei Lin,Li, Yu Chen,Sun, Meng Ru,Wang, Yitao,Wang, Shengpeng,Yang, Hua,Liu, Bao Lin,Wang, Mei,Gao, Wen,&Li, Ping.(2022).Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium.Antioxidants,11(4).
MLA Li, Yi,et al."Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium".Antioxidants 11.4(2022).
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