Premium
Dammarenediol‐II Prevents VEGF‐Mediated Microvascular Permeability in Diabetic Mice
Author(s) -
Kim SuHyeon,
Jung SeHui,
Lee YeonJu,
Han Jung Yeon,
Choi YongEui,
Hong HaeDeun,
Jeon HyeYoon,
Hwang JongYun,
Na SungHun,
Kim YoungMyeong,
Ha KwonSoo
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5480
Subject(s) - vegf receptors , vascular permeability , pharmacognosy , permeability (electromagnetism) , angiogenesis , pharmacology , vascular endothelial growth factor , medicine , chemistry , traditional medicine , endocrinology , biological activity , in vitro , biochemistry , membrane
Diabetic retinopathy is a major diabetic complication predominantly caused by vascular endothelial growth factor (VEGF)‐induced vascular permeability in the retina; however, treatments targeting glycemic control have not been successful. Here, we investigated the protective effect of dammarenediol‐II, a precursor of triterpenoid saponin biosynthesis, on VEGF‐induced vascular leakage using human umbilical vein endothelial cells (HUVECs) and diabetic mice. We overproduced the compound in transgenic tobacco expressing Panax ginseng dammarenediol‐II synthase gene and purified using column chromatography. Analysis of the purified compound using a gas chromatography–mass spectrometry system revealed identical retention time and fragmentation pattern to those of authentic standard dammarenediol‐II. Dammarenediol‐II inhibited VEGF‐induced intracellular reactive oxygen species generation, but it had no effect on the levels of intracellular Ca 2+ in HUVECs. We also found that dammarenediol‐II inhibited VEGF‐induced stress fiber formation and vascular endothelial‐cadherin disruption, both of which play critical roles in modulating endothelial permeability. Notably, microvascular leakage in the retina of diabetic mice was successfully inhibited by intravitreal dammarenediol‐II injection. Our results suggest that the natural drug dammarenediol‐II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy. Copyright © 2015 John Wiley & Sons, Ltd.