Angiogenic ginsenoside F1 and Rh1 inhibit vascular permeability via regulating NR4A1 = 혈관신생 진세노사이드 F1과 Rh1의 NR4A1 조절을 통한 혈관누수억제 기능에 관한 연구

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Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is an essential process in human physiology and disease pathology. In ischemic disease condition, VEGF-induced angiogenesis is often accompanied by a vascular permeability response. Therefore, the proper induction of angiogenesis without vascular leakage will be crucial for its effective therapy. Ginsenosides, triterpenoid saponins, are derived from the well-known medicinal plant, Panax ginseng (commonly known as ginseng), and have been considered candidates for modulating angiogenesis. Here, we examined the angiogenic effects of 10 different ginsenosides on human umbilical vein endothelial cells (HUVECs) and validated first time that two protopanaxatriol (PPT)-type ginsenosides, F1 and Rh1 could promote the tube formation, migration, and proliferation of endothelial cells (ECs). Interestingly, RNA transcriptome analysis showed that gene regulation induced by VEGF in ECs is distinct from that of ginsenosides F1 and Rh1. Unlike VEGF, F1 and Rh1 do not induce vascular permeability both in vitro and in vivo. In addition, F1 and Rh1 significantly inhibited VEGF-induced vascular permeability. Comparative transcriptome analysis revealed that these effects of F1 and Rh1 on vascular leakage restoration are mainly caused by the changes in VEGF-mediated tumor necrosis factor alpha ($TNF\alpha$) signaling via nuclear factor kappa-light-chain-enhancer of activated B cells ($NF\kappaB$). Particularly, the expression and transcription activity of nuclear receptor subfamily 4 group A member 1 (NR4A1) in $TNF\alpha$ signaling via $NF\kappaB$ were suppressed by F1 and Rh1. By modulating NR4A1, F1 and Rh1 could stabilize the expression and localization of junctional vascular endothelial (VE)-cadherin, which plays an important role in regulating vascular leakage. These findings demonstrate that ginsenosides F1 and Rh1 can be promising herbal remedies for vessel normalization in ischemic disease and that NR4A1 is the key target.
Kim, Ho Minresearcher김호민researcher
한국과학기술원 :의과학학제전공,
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학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2019.2,[vi, 65 p. :]


ginsenoside F1▼aginsenoside Rh1▼aangiogenesis▼avascular permeability▼aNR4A1; 진세노사이드 F1▼a진세노사이드 Rh1▼a혈관신생▼a혈관누수억제▼aNR4A1

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