PMID- 24127121
OWN - NLM
STAT- MEDLINE
DCOM- 20141103
LR  - 20231213
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 37
IP  - 2
DP  - 2014 Apr
TI  - Piperlonguminine downregulates endothelial protein C receptor shedding in vitro 
      and in vivo.
PG  - 435-42
LID - 10.1007/s10753-013-9756-2 [doi]
AB  - Endothelial cell protein C receptor (EPCR) plays an important role in coagulation 
      and inflammation. EPCR can be shed from the cell surface, and this is mediated by 
      tumor necrosis factor-alpha-converting enzyme (TACE). Piperlonguminine (PL), an 
      important component of Piper longum fruits, is known to exhibit 
      antihyperlipidemic, antiplatelet, and antimelanogenesis activities. However, 
      little is known about the effects of PL on EPCR shedding. Here, we investigated 
      this issue by monitoring the effects of PL on phorbol-12-myristate 13-acetate 
      (PMA) and on cecal ligation and puncture (CLP)-mediated EPCR shedding and 
      underlying mechanisms. PL induced potent inhibition of PMA, and CLP induced EPCR 
      shedding through suppression of TACE expression. And treatment with PL resulted 
      in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases 
      (ERK) 1/2, and c-Jun N-terminal kinase (JNK). Given these results, PL might have 
      potential 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, Republic of Korea.
FAU - Kim, Jeong Ah
AU  - Kim JA
FAU - Bae, Jong-Sup
AU  - Bae JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antigens, CD)
RN  - 0 (Dioxolanes)
RN  - 0 (Endothelial Protein C Receptor)
RN  - 0 (Interleukin-6)
RN  - 0 (PROCR protein, human)
RN  - 0 (Plant Extracts)
RN  - 0 (Procr protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
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  - SGD66V4SVJ (piperlongumine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - ADAM Proteins/metabolism
MH  - ADAM17 Protein
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antigens, CD/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Dioxolanes/*pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Protein C Receptor
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fruit
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphorylation
MH  - Phytotherapy
MH  - Piper
MH  - Plant Extracts/*pharmacology
MH  - Plants, Medicinal
MH  - Receptors, Cell Surface/*drug effects/metabolism
MH  - Sepsis/*drug therapy/metabolism/microbiology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2013/10/16 06:00
MHDA- 2014/11/05 06:00
CRDT- 2013/10/16 06:00
PHST- 2013/10/16 06:00 [entrez]
PHST- 2013/10/16 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
AID - 10.1007/s10753-013-9756-2 [doi]
PST - ppublish
SO  - Inflammation. 2014 Apr;37(2):435-42. doi: 10.1007/s10753-013-9756-2.