title: Ginsenoside Rb1 ameliorates lipopolysaccharide-induced albumin leakage from rat mesenteric venules by intervening in both trans- and paracellular pathway.
abstract: Lipopolysaccharide (LPS) is one of the common pathogens that causes mesentery hyperpermeability- and intestinal edema-related diseases. This study evaluated whether ginsenoside Rb1 (Rb1), an ingredient of a Chinese medicine Panax ginseng, has beneficial effects on mesentery microvascular hyperpermeability induced by LPS and the underlying mechanisms. Male Wistar rats were continuously infused with LPS (5 mg · kg(-1) · h(-1)) via the left jugular vein for 90 min. In some rats, Rb1 (5 mg · kg(-1) · h(-1)) was administrated through the left jugular vein 30 min after LPS infusion. The dynamics of fluorescein isothiocynate-labeled albumin leakage from mesentery venules was assessed by intravital microscopy. Intestinal tissue edema was evaluated by hematoxylin and eosin staining. The number of caveolae in endothelial cells of microvessels was examined by electron microscopy. Confocal microscopy and Western blotting were applied to detect caveolin-1 (Cav-1) expression and phosphorylation, junction-related proteins, and concerning signaling proteins in intestinal tissues and human umbilical vein endothelial cells. LPS infusion evoked an increased albumin leakage from mesentery venules that was significantly ameliorated by Rb1 posttreatment. Mortality and intestinal edema around microvessels were also reduced by Rb1. Rb1 decreased caveolae number in endothelial cells of microvessels. Cav-1 expression and phosphorylation, VE-Cadherin phosphorylation, ZO-1 degradation, nuclear factor-κB (NF-κB) activation, and Src kinase phosphorylation were inhibited by Rb1. Rb1 ameliorated microvascular hyperpermeability after the onset of endotoxemia and improved intestinal edema through inhibiting caveolae formation and junction disruption, which was correlated to suppression of NF-κB and Src activation.
authors.affiliation: Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China;
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Yun-Pei
authors.initials: YP
authors.lastname: Zhang
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Chang
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.forename: Ke
authors.initials: K
authors.lastname: He
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Mao
authors.forename: Lei
authors.initials: L
authors.lastname: Tu
authors.forename: Chuan-She
authors.initials: CS
authors.lastname: Wang
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014699:Venules / Q000187:drug effects / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051242:Caveolin 1; D036145:Ginsenosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D019061:src-Family Kinases; D000099152:Cadherin 5; C495540:CAV1 protein, human; C569042:TJP1 protein, human; C482199:lipopolysaccharide, E coli O55-B5; C442759:ginsenoside Rb1
keywords: Panax ginseng; Src; caveolin-1; hyperpermeability; nuclear factor-κB