PMID- 24286327 OWN - NLM STAT- MEDLINE DCOM- 20150204 LR - 20211021 IS - 1976-670X (Electronic) IS - 1976-6696 (Print) IS - 1976-6696 (Linking) VI - 47 IP - 6 DP - 2014 Jun TI - Inhibitory effects of oroxylin A on endothelial protein C receptor shedding in vitro and in vivo. PG - 336-41 AB - Endothelial cell protein C receptor (EPCR) plays important roles in blood coagulation and inflammation. EPCR activity is markedly changed by ectodomain cleavage and release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-alpha converting enzyme (TACE). Oroxylin A (OroA), a major component of Scutellaria baicalensis Georgi, is known to exhibit anti-angiogenic, antiinflammation, and anti-invasive activities. However, little is known about the effects of OroA on EPCR shedding. Data showed that OroA induced potent inhibition of phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and on cecal ligation and puncture (CLP)-induced EPCR shedding through suppression of TACE expression and activity. In addition, treatment with OroA resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results demonstrate the potential of OroA as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding. FAU - Ku, Sae-Kwang AU - Ku SK AD - Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. FAU - Han, Min-Su AU - Han MS AD - Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital, Daegu 701-724, Korea. FAU - Lee, Min Young AU - Lee MY AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea. FAU - Lee, You-Mie AU - Lee YM AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea. FAU - Bae, Jong-Sup AU - Bae JS AD - College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Korea (South) TA - BMB Rep JT - BMB reports JID - 101465334 RN - 0 (Blood Coagulation Factors) RN - 0 (Flavonoids) RN - 0 (Interleukin-1beta) RN - 0 (Receptors, Cell Surface) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (activated protein C receptor) RN - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.86 (ADAM17 Protein) RN - EC 3.4.24.86 (ADAM17 protein, human) RN - EC 3.4.24.86 (Adam17 protein, mouse) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - ADAM Proteins/metabolism MH - ADAM17 Protein MH - Animals MH - Blood Coagulation Factors/*metabolism MH - Disease Models, Animal MH - Down-Regulation/*drug effects MH - Flavonoids/chemistry/*pharmacology/therapeutic use MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Interleukin-1beta/pharmacology MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Phosphorylation/drug effects MH - Receptors, Cell Surface/*metabolism MH - Scutellaria baicalensis/chemistry/metabolism MH - Sepsis/drug therapy/etiology/metabolism MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC4163868 EDAT- 2013/11/30 06:00 MHDA- 2015/02/05 06:00 PMCR- 2014/07/01 CRDT- 2013/11/30 06:00 PHST- 2013/09/02 00:00 [received] PHST- 2013/11/30 06:00 [entrez] PHST- 2013/11/30 06:00 [pubmed] PHST- 2015/02/05 06:00 [medline] PHST- 2014/07/01 00:00 [pmc-release] AID - 2499 [pii] AID - BMB-47-336 [pii] AID - 10.5483/bmbrep.2014.47.6.198 [doi] PST - ppublish SO - BMB Rep. 2014 Jun;47(6):336-41. doi: 10.5483/bmbrep.2014.47.6.198.