PMID- 29594285
OWN - NLM
STAT- MEDLINE
DCOM- 20180925
LR  - 20211204
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 9
IP  - 4
DP  - 2018 Apr 25
TI  - Paeoniflorin prevents endoplasmic reticulum stress-associated inflammation in 
      lipopolysaccharide-stimulated human umbilical vein endothelial cells via the 
      IRE1alpha/NF-kappaB signaling pathway.
PG  - 2386-2397
LID - 10.1039/c7fo01406f [doi]
AB  - Endoplasmic reticulum (ER) stress-associated inflammation is a critical molecular 
      mechanism involved in the pathogenesis of endothelial dysfunction (ED). Hence, 
      strategies for alleviating ER stress-induced inflammation may be essential for 
      the prevention of cardiovascular diseases. Paeoniflorin (PF), a bioactive 
      compound from Paeonia lactiflora Pallas is known for its functional properties 
      against vascular inflammation. However, to date, PF-mediated protection against 
      ER stress-dependent inflammation has not been identified. Herein, we investigate 
      the protective effect of PF on lipopolysaccharide (LPS)-stimulated human 
      umbilical vein endothelial cell (HUVEC) injury and explore its underlying 
      mechanism. The result of the cell viability assay indicates that PF promotes the 
      cell survival rate in LPS-stimulated HUVECs. In addition, the LPS-induced 
      over-production of inflammatory cytokines (interleukin-6 (IL-6) and monocyte 
      chemotactic protein 1 (MCP-1)) and ER stress markers (78 kDa glucose regulated 
      protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)) are 
      significantly decreased by PF and the ER stress inhibitor 4-phenylbutric acid 
      (4-PBA). The transmission electron microscopy (TEM) assay implies that the 
      ultrastructural abnormalities in ER are reversed by PF treatment, which is 
      similar to the protective effect of 4-PBA. Impressively, we find that the 
      inositol-requiring enzyme 1alpha (IRE1alpha)/nuclear factor-kappa B (NF-kappaB) pathway is 
      significantly activated and contributes to the progress of LPS-induced HUVEC 
      injury by promoting inflammatory cytokine production. IRE1alpha siRNA, AEBSF (ATF6 
      inhibitor), GSK2656157 (PERK inhibitor), PDTC (NF-kappaB inhibitor) and thapsigargin 
      (TG, IRE1 activator) are used to confirm the role of the IRE1alpha/NF-kappaB pathway in 
      PF-mediated protection against LPS-induced HUVEC injury. Our findings indicate 
      that PF has an inhibitory effect on endothelial injury. To summarize, PF might be 
      a potential therapeutic agent to inhibit ER stress-associated vascular 
      inflammation.
FAU - Chen, Juan
AU  - Chen J
AD  - School of Life Sciences, Anhui University, Hefei 230601, PR China.
FAU - Zhang, Minghua
AU  - Zhang M
FAU - Zhu, Maomao
AU  - Zhu M
FAU - Gu, Junfei
AU  - Gu J
FAU - Song, Jie
AU  - Song J
FAU - Cui, Li
AU  - Cui L
FAU - Liu, Dan
AU  - Liu D
FAU - Ning, Qing
AU  - Ning Q
FAU - Jia, Xiaobin
AU  - Jia X
FAU - Feng, Liang
AU  - Feng L
LA  - eng
PT  - Journal Article
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Chemokine CCL2)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Glucosides)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Monoterpenes)
RN  - 0 (NF-kappa B)
RN  - 21AIQ4EV64 (peoniflorin)
RN  - EC 2.7.11.1 (ERN1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.- (Endoribonucleases)
SB  - IM
MH  - Chemokine CCL2/genetics/metabolism
MH  - Drugs, Chinese Herbal/*pharmacology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Endoribonucleases/genetics/*metabolism
MH  - Glucosides/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Interleukin-6/genetics/metabolism
MH  - Lipopolysaccharides/adverse effects
MH  - Monoterpenes/*pharmacology
MH  - NF-kappa B/genetics/*metabolism
MH  - Paeonia/*chemistry
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Signal Transduction/*drug effects
EDAT- 2018/03/30 06:00
MHDA- 2018/09/27 06:00
CRDT- 2018/03/30 06:00
PHST- 2018/03/30 06:00 [pubmed]
PHST- 2018/09/27 06:00 [medline]
PHST- 2018/03/30 06:00 [entrez]
AID - 10.1039/c7fo01406f [doi]
PST - ppublish
SO  - Food Funct. 2018 Apr 25;9(4):2386-2397. doi: 10.1039/c7fo01406f.