title: Anti-vascular inflammatory effects of pentacyclic triterpenoids from Astilbe rivularis in vitro and in vivo.
abstract: Sepsis is a systemic inflammatory condition resulting from bacterial infections. It is associated with high mortality rates, and its therapeutic options are limited. Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein that functions as a mediator of experimental sepsis. C-27-carboxylated pentacyclic triterpenoids are specifically found in species of the genus Astilbe, and show several biological effects. Given the anti-inflammatory effects of pentacyclic triterpenoids, we investigated the effects of 3β-trans-p-coumaroyloxy-olean-12-en-27-oic acid (1) and 6β-hydroxy-3-oxoolean-12-en-27-oic acid (2) on TGFBIp-mediated vascular inflammatory responses. The anti-inflammatory activities of compounds 1 and 2 were determined by measuring the permeability, leukocyte adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated human umbilical vein endothelial cells (HUVECs) and mice. We found that compounds 1 and 2 inhibited lipopolysaccharide (LPS)-induced TGFBIp secretion, TGFBIp-induced barrier disruption, expression of cell adhesion molecules (CAMs), and the adhesion/transendothelial migration of the neutrophils to the human endothelial cells. Compounds 1 and 2 also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggested that C-27-carboxylated pentacyclic triterpenoids 1 and 2 have anti-inflammatory functions by inhibiting hyperpermeability, CAM expression, and leukocyte adhesion/migration. Therefore, these compounds can be considered as a potential therapy for vascular inflammatory diseases.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: Cancer Control Team, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea.
authors.forename: Jongdoo
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Jiwoo
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Herbal Formulation, MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 3861, Republic of Korea.
authors.forename: Sang Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yanbian University, Yanji 133002, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: mkna@cnu.ac.kr.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002432:Cecum / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011677:Punctures; D031995:Saxifragaceae / Q000737:chemistry*; D018805:Sepsis / Q000188:drug therapy / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D020011:Protective Agents; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099222:betaIG-H3 Protein
keywords: Astilbe rivularis; C-27 Carboxylated pentacyclic triterpenoids; Inflammation; Sepsis; TGFBIp