title: Rk1, a ginsenoside, is a new blocker of vascular leakage acting through actin structure remodeling.
abstract: Endothelial barrier integrity is essential for vascular homeostasis and increased vascular permeability and has been implicated in many pathological processes, including diabetic retinopathy. Here, we investigated the effect of Rk1, a ginsenoside extracted from sun ginseng, on regulation of endothelial barrier function. In human retinal endothelial cells, Rk1 strongly inhibited permeability induced by VEGF, advanced glycation end-product, thrombin, or histamine. Furthermore, Rk1 significantly reduced the vessel leakiness of retina in a diabetic mouse model. This anti-permeability activity of Rk1 is correlated with enhanced stability and positioning of tight junction proteins at the boundary between cells. Signaling experiments revealed that Rk1 induces phosphorylation of myosin light chain and cortactin, which are critical regulators for the formation of the cortical actin ring structure and endothelial barrier. These findings raise the possibility that ginsenoside Rk1 could be exploited as a novel prototype compound for the prevention of human diseases that are characterized by vascular leakage.
authors.affiliation: Department of Biochemistry College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Maeng
authors.forename: Sony
authors.initials: S
authors.lastname: Maharjan
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jeong-Hill
authors.initials: JH
authors.lastname: Park
authors.forename: Young
authors.initials: Y
authors.lastname: Suk Yu
authors.forename: Young-Myoung
authors.initials: YM
authors.lastname: Kim
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D018994:Myosin Light Chains / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012160:Retina / Q000166:cytology; D013917:Thrombin / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D000199:Actins; D051356:Cortactin; D036145:Ginsenosides; D017127:Glycation End Products, Advanced; D018994:Myosin Light Chains; D042461:Vascular Endothelial Growth Factor A; C472077:ginsenoside Rk1; D006632:Histamine; D013917:Thrombin
references.citation: J Cell Physiol. 1996 Jun;167(3):562-9
references.pmid: 8655610
references.citation: Circulation. 2004 Sep 7;110(10):1219-25
references.pmid: 15337705
references.citation: Br J Pharmacol. 2007 Sep;152(2):172-4
references.pmid: 17603551
references.citation: Nature. 2005 Sep 22;437(7058):497-504
references.pmid: 16177780
references.citation: Biochem Biophys Res Commun. 2006 Oct 27;349(3):987-94
references.pmid: 16962070
references.citation: Biochem Pharmacol. 2006 Aug 14;72(4):437-45
references.pmid: 16793023
references.citation: J Cell Biochem. 2004 Aug 15;92(6):1075-85
references.pmid: 15258893
references.citation: J Chromatogr A. 2001 Jul 6;921(2):335-9
references.pmid: 11471818
references.citation: FASEB J. 2005 Nov;19(13):1845-7
references.pmid: 16160062
references.citation: Mutat Res. 2003 Feb-Mar;523-524:63-74
references.pmid: 12628504
references.citation: J Biol Chem. 2004 Jun 4;279(23):24692-700
references.pmid: 15056655
references.citation: Ann N Y Acad Sci. 2008 Mar;1123:134-45
references.pmid: 18375586
references.citation: Oncogene. 2001 Oct 1;20(44):6418-34
references.pmid: 11607842
references.citation: Angiogenesis. 2007;10(2):103-17
references.pmid: 17340211
references.citation: Diabetes. 1999 Oct;48(10):2052-8
references.pmid: 10512373
references.citation: Curr Opin Crit Care. 2008 Feb;14(1):22-30
references.pmid: 18195622
references.citation: Br J Pharmacol. 2007 Sep;152(2):207-15
references.pmid: 17603552
references.citation: Physiol Rev. 1999 Jul;79(3):703-61
references.pmid: 10390517
references.citation: Am Fam Physician. 2003 Oct 15;68(8):1539-42
references.pmid: 14596440
references.citation: Ophthalmic Res. 1995;27(1):48-52
references.pmid: 7596559
references.citation: Biol Pharm Bull. 1994 May;17(5):635-9
references.pmid: 7522731
references.citation: J Cell Sci. 2001 Apr;114(Pt 7):1343-55
references.pmid: 11257000
references.citation: J Cell Biol. 1998 Apr 6;141(1):199-208
references.pmid: 9531559
references.citation: Mutagenesis. 2005 Jul;20(4):237-43
references.pmid: 15956041
references.citation: Am J Physiol. 1992 Apr;262(4 Pt 2):H1238-47
references.pmid: 1566906
references.citation: Am J Physiol. 1995 Oct;269(4 Pt 1):G467-75
references.pmid: 7485497
references.citation: Cancer Lett. 2000 Mar 13;150(1):41-8
references.pmid: 10755385
references.citation: J Clin Invest. 2001 Sep;108(5):689-701
references.pmid: 11544274
references.citation: Nature. 2000 Dec 7;408(6813):732-5
references.pmid: 11130076
references.citation: Int J Biochem Cell Biol. 2004 Jul;36(7):1206-37
references.pmid: 15109567
references.citation: J Cell Physiol. 1986 Jul;128(1):96-104
references.pmid: 3722274
references.citation: J Cell Biol. 1999 Dec 27;147(7):1569-82
references.pmid: 10613913
references.citation: Physiol Rev. 2006 Jan;86(1):279-367
references.pmid: 16371600
references.citation: J Appl Physiol (1985). 2001 Oct;91(4):1487-500
references.pmid: 11568129
references.citation: Przegl Lek. 2005;62(4):238-42
references.pmid: 16229243
references.citation: N Engl J Med. 1988 May 19;318(20):1315-21
references.pmid: 3283558
references.citation: J Cell Biol. 1999 Dec 13;147(6):1351-63
references.pmid: 10601346
references.citation: FASEB J. 2002 Jul;16(9):950-62
references.pmid: 12087056
references.citation: Nature. 2005 Dec 15;438(7070):960-6
references.pmid: 16355161
references.citation: N Engl J Med. 2004 Jan 1;350(1):48-58
references.pmid: 14702427
references.citation: Annu Rev Physiol. 1998;60:143-59
references.pmid: 9558458
references.citation: Vascul Pharmacol. 2002 Nov;39(4-5):187-99
references.pmid: 12747959