Inhibitory effects of pentacyclic triterpenoids from Astilbe rivularis on TGFBIp-induced inflammatory responses in vitro and in vivo.
Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein which expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs), and functions as a mediator of experimental sepsis. Pentacyclic triterpenoids bearing a carboxyl group at C-27 position, 3β,6α-dihydroxyolup-20(29)-ene (1), 3β,6β-dihydroxyolean-12-en-27-oic acid (2) and 3β,24-dihydroxyolean-12-en-27-oic acid (3), are representative bioactive molecules in the genus Astilbe that possess cytotoxic, anti-inflammatory and wounds healing activities. Based on the biological effects of C-27 carboxylated pentacyclic triterpenoids, we investigated the anti-inflammatory effects of compounds 1-3 against TGFBIp-mediated vascular inflammatory responses. The anti-inflammatory activities of compounds 1-3 were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated human HUVECs and mice. We found that compounds 1-3 inhibited TGFBIp-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of neutrophils to human endothelial cells. Each compound also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggest that compounds 1-3 possess anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.
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.
Byeongjin
B
Jung
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.
Jiwoo
J
Chung
College of Pharmacy, Yanbian University, Yanji 133002, People's Republic of China.
Wei
W
Zhou
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.
Taeho
T
Lee
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: mkna@cnu.ac.kr.
MinKyun
M
Na
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.
Jong-Sup
JS
Bae
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039641:Integrin beta Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010539:Permeability / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D031995:Saxifragaceae / Q000737:chemistry* / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000099222:betaIG-H3 Protein
D000410:Alanine Transaminase; D000893:Anti-Inflammatory Agents; D001219:Aspartate Aminotransferases; D016326:Extracellular Matrix Proteins; D024243:HMGB1 Protein; D039641:Integrin beta Chains; D009828:Oleanolic Acid; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D014315:Triterpenes; D019010:Vascular Cell Adhesion Molecule-1; D000099222:betaIG-H3 Protein; C000613757:3,24-dihydroxyolean-12-en-27-oic acid; C000613756:3,6-dihydroxyolup-20(29)-ene; C494851:3beta,6beta-dihydroxyolean-12-en-27-oic acid
Astilbe rivularis; Inflammation; Pentacyclic triterpenoids; Sepsis; TGFBIp