PMID- 29518395 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20180910 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 826 DP - 2018 May 5 TI - Oridonin inhibits vascular inflammation by blocking NF-kappaB and MAPK activation. PG - 133-139 LID - S0014-2999(18)30128-6 [pii] LID - 10.1016/j.ejphar.2018.02.044 [doi] AB - Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-kappaB p65 translocation was measured by immunofluorescence. Acute lung inflammation model was used to evaluate leukocyte infiltration in vivo. The endothelial-leukocyte adhesion and the leukocyte transmigration were profoundly reduced by oridonin. Oridonin dramatically inhibited the expression of TNF-alpha-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1(MCP-1)). Oridonin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, Oridonin also suppressed the TNF-alpha-activated MAPK and Nuclear factor kappa B (NF-kappaB) activation. Our results suggest that oridonin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of MAPK and NF-kappaB activation, which may have a potential therapeutic use for inflammatory vascular diseases. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Huang, Weichen AU - Huang W AD - Department of the first Orthopedics, The 2nd Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, Guizhou, China. Electronic address: huangweichen1573@sina.com. FAU - Huang, Mingcheng AU - Huang M AD - Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Ouyang, Hui AU - Ouyang H AD - Department of Gastroenterology, The 7th Affiliated Hospital, Sun Yat-Sen University, ShenZhen, Guandong, China. FAU - Peng, Jingwen AU - Peng J AD - Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, SunYat-sen University, Guangzhou, Guandong, China. FAU - Liang, Jiang AU - Liang J AD - Collaborative innovation center of Miao medicine, Guiyang College of Traditional Chinese Medicine, Guiyang, Guizhou, China. Electronic address: liangjiang1573@hotmail.com. LA - eng PT - Journal Article DEP - 20180305 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Diterpenes, Kaurane) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0APJ98UCLQ (oridonin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology/therapeutic use MH - Cell Adhesion/drug effects MH - Cell Communication/drug effects MH - Cells, Cultured MH - Disease Models, Animal MH - Diterpenes, Kaurane/*pharmacology/therapeutic use MH - Endothelium, Vascular/*drug effects/immunology/pathology MH - Humans MH - MAP Kinase Signaling System/*drug effects/immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/physiology MH - NF-kappa B/immunology/metabolism MH - Pneumonia/*drug therapy/immunology/pathology MH - Reactive Oxygen Species/metabolism MH - Recombinant Proteins/administration & dosage/immunology MH - Tumor Necrosis Factor-alpha/administration & dosage/immunology OTO - NOTNLM OT - Endothelial cells OT - Oridonin OT - Vascular inflammation EDAT- 2018/03/09 06:00 MHDA- 2018/09/11 06:00 CRDT- 2018/03/09 06:00 PHST- 2018/02/05 00:00 [received] PHST- 2018/02/22 00:00 [revised] PHST- 2018/02/27 00:00 [accepted] PHST- 2018/03/09 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2018/03/09 06:00 [entrez] AID - S0014-2999(18)30128-6 [pii] AID - 10.1016/j.ejphar.2018.02.044 [doi] PST - ppublish SO - Eur J Pharmacol. 2018 May 5;826:133-139. doi: 10.1016/j.ejphar.2018.02.044. Epub 2018 Mar 5.