Paeonol from Paeonia suffruticosa prevents TNF-α-induced monocytic cell adhesion to rat aortic endothelial cells by suppression of VCAM-1 expression

Pan, Lingyu; Dai, Min

doi:10.1016/j.phymed.2009.04.003

Cited by 57 publications

(42 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vitro, paeonol reduces the formation of ox-LDL lesions by inhibiting lipid peroxidation and down-regulating VCAM-1 expression against tumor necrosis factor alpha (TNF-α). 14,15) These molecular mechanisms may be due to paeonol antioxidative, 16) anti-inflammatory 17) and antithrombotic activities. 18) In short, the current study was carried out to evaluate the potential protective effect of paeonol on AS and determine its possible mechanisms on MAPK pathways.…”

mentioning

confidence: 99%

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Wang

Dai

Zhong

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Atherosclerosis is a chronic inflammatory disease characterized by increased expression of adhesion molecules, which contribute to monocytes adhesion to vascular endothelial cells (VECs). Paeonol, an active compound isolated from cortex Moutan, has been shown to have therapeutic effects on atherosclerotic animals. The present study aims to investigate whether paeonol can inhibit monocyte adhesion to vascular endothelial cells induced by oxidized Low-Density Lipoprotein (ox-LDL) and its possible therapeutic molecular mechanism. Exposure to ox-LDL (50, 100 µg/mL) induced damaged to VECs leading to decreased survival rates (p<0.01). Paeonol (7.2-18.0 µM) partially restored survival and reduced lactate dehydrogenase (LDH) release in VECs in a concentration-dependent manner (p<0.01). Adhesion of monocytes to VECs was dramatically prevented by paeonol at 21.6 and 25.2 μM (p<0.01). In addition, paeonol (14.4-21.6 μM) repressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and lowered the levels of phosphor-c-Jun N-terminal kinase (P-JNK)1/2, phosphor-extracellular signal-regulated kinase (P-ERK)1/2 and P-p38 in a dose-dependent manner. The molecular effects of paeonol were more pronouced when companied with mitogen activated protein kinases (MAPKs) inhibitors. These data suggest that paeonol (10.8-25.2 μM), at certain concentrations, prevents monocyte adhesion to VEC induced by ox-LDL, probably by means of blocking one or more target proteins on MAPKs signaling pathway. These results indicate that paeonol has potential protective effects on the development of atherosclerosis.

show abstract

mentioning

confidence: 99%

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Wang

Dai

Zhong

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Our previous investigations have indicated that its anti-atherosclerotic effects are associated with protection of endothelial cells from injury [5,11] . However, the underlying mechanisms are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…A large number of studies have demonstrated that paeonol is effective for preventing and treating of AS in experimental models by modulating inflammatory reactions during the initiation and development of AS. For example, paeonol inhibits tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression, which reduces monocyte adhesion to VECs [5] . Moreover, paeonol suppresses lipopolysaccharide-induced inflammatory cytokine release from macrophage cells and protects mice from lethal endotoxin shock [6] .…”

Section: Introductionmentioning

confidence: 99%

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

Liu¹,

Chen²,

Dai

2014

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Paeonol (2′-hydroxy-4′-methoxyacetophenone) from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells (VECs) in vitro. Methods: VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA. Results: Ox-LDL treatment inhibited VEC growth in dose-and time-dependent manners (the value of IC 50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L) significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose-and time-dependent manners. Moreover, paeonol (120 μmol/ L) prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN's 3'-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment. Conclusion: miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis.

show abstract

“…The dyed leukocytes (100 ml) were added to each well to adhere with HUVECs for 1 h. The well was washed three times to remove unbound cells. Then cells were treated with a solution of ethanol/ PBS (1:1) 100 ml for 1 h to release the stain [Basoni et al, 2005;Pan and Dai, 2009]. Absorbance at 570 nm for each well was determined by a model 1500 Multiskan spectrum microplate reader.…”

Section: Adhesion Test By Colorimetric Assaymentioning

confidence: 99%

“…BCECF-AM solution was then added into the leukocytes suspension with the final concentration of 3 mM. The mixture was then incubated at 371C for 1 h. Stained leukocytes (3 Â 10 6 cells/ml, 100 ml) were added to each well to adhere with HUVECs for 1 h. The well was washed to remove nonadherent cells [Pan and Dai, 2009]. …”

Section: Adhesion Test By Fluorometric Assaymentioning

confidence: 99%

Peoniflorin prevents the adhesion between inflammatory endothelial cells and leukocytes through inhibiting the activation of MAPKs and NF‐κB

Gao

Song

et al. 2010

Drug Development Research

View full text Add to dashboard Cite

The vascular endothelium can be activated by multiple factors, including lipopolysaccharide (LPS) functioning as a key component of the inflammatory response. Activated endothelium promotes the recruitment of leukocytes mainly by releasing various adhesion molecules and amplifies inflammation via a feedback loop. Peoniflorin, the main active constituent of the roots of Paeonia lactiora Pall., possesses anti-inammatory, anti-infective, and anti-platelet aggregative properties. To elucidate the anti-inammatory mechanism of peoniflorin, the present study was conducted to address its effects on the adhesion of inflammatory endothelial cells to leukocytes. Peoniflorin substantially reduced adhesion of either human acute monocytic leukemia cells (THP-1) or human acute promyelocytic leukemia cells (HL-60) to LPS-stimulated human umbilical vein endothelial cells (HUVECs). It also markedly down-regulated the expression of E-selectin at both the gene and protein levels. However, peoniflorin only slightly reduced expression of intercellular adhesion molecule-1 (ICAM-1). Signal pathway analysis indicated that peoniflorin reduced phosphorylation of c-Jun NH 2 -terminal kinase (JNK) and p38 kinase, as well as the phosphorylation and degradation of IkB-a in HUVECs. These findings suggest that prevention of the adhesion between inflammatory endothelial cells and leukocytes contributes, at least partially, to the anti-inflammation action of peoniflorin. The anti-adhesion Abbreviations used: LPS, lipopolysaccharide; GPL, glycosides isolated from the roots of Paeonia lactiora Pall.; HUVECs, human umbilical vein endothelial cells; HL-60, human acute promyelocytic leukemia cell line; THP-1, human acute monocytic leukemia cell line; MAPK, mitogen-activated protein kinase; JNK, c-Jun NH 2 -terminal kinase; ERK, extracellular signal-regulated kinase; NF-kB, nuclear factor-kappa B; ICAM-1, intercellular adhesion molecule-1; BCECF-AM, Bis-carboxyethyl-carboxyfluorescein acetoxy-methyl; DEX, dexamethasone; NBCS, newborn calf serum; TLR4, toll-like receptor 4; MD2, myeloid differentiation protein-2; IkB, inhibitor of kB.c 2010 Wiley-Liss, Inc.mechanisms of peoniflorin were involved in the down-regulation of the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kB), and a reduction of adhesion molecule expressions in endothelial cells. Drug Dev Res 71: 275-284, 2010.

show abstract

Paeonol from Paeonia suffruticosa prevents TNF-α-induced monocytic cell adhesion to rat aortic endothelial cells by suppression of VCAM-1 expression

Cited by 57 publications

References 17 publications

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Paeonol Inhibits Oxidized Low Density Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelial Cells by Inhibiting the Mitogen Activated Protein Kinase Pathway

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

Peoniflorin prevents the adhesion between inflammatory endothelial cells and leukocytes through inhibiting the activation of MAPKs and NF‐κB

Contact Info

Product

Resources

About