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

Abstract

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.

Protective effects of peoniflorin against hydrogen peroxide-induced oxidative stress in human umbilical vein endothelial cells

“…In addition, our previous study , together with the study by Xu et al (2010), has indicated the antiinflammatory effects of PF in endothelial cells, namely by blocking adhesion molecules and chemokine production. Moreover, endothelial inflammation and oxidative stress are vital in the pathogenesis of various vascular diseases, such as cutaneous vasculitis.…”

Paeoniflorin protects against lipopolysaccharide-induced acute lung injury in mice by alleviating inflammatory cell infiltration and microvascular permeability

“…PF pretreatment could suppress MPO activity in lung tissues. Considering that leukocyte-endothelial interaction is essential for PMN recruitment to lung tissues, our previous findings that PF could prevent the adhesion of inflammatory endothelial cells to different kinds of leukocytes may provide a plausible explanation for PF attenuating the infiltration of PMNs [13]. Furthermore, disruption of vascular barrier integrity will lead to increased permeability of fluid and respiratory failure [28].…”

“…Paeoniflorin (PF), the major active constituent of TGP, has been reported to have many pharmacological effects, such as antiallergic [7], antiarthritic [8], hepatoprotective [9], and analgesic [10]. Recently, it was documented to be able to inhibit the properties systemic inflammatory responses in cecal ligation and puncture-induced sepsis [11], a main reason for ALI, protect against lipopolysaccharide (LPS)-induced liver inflammation, and prevent the adhesion between LPS-induced inflammatory endothelial cells and leukocytes [12,13]. Furthermore, it was proven to exhibit inhibitory effects on neuroinflammation, and analgesic effects through activating adenosine A1 receptor [14,15], which is beneficial for reducing PMN cell trafficking and microvascular permeability in LPS-induced lung injury [3].…”

Therapeutic potential of paeoniflorin in atherosclerosis: A cellular action and mechanism-based perspective

“…Not coincidentally, Xu et al. ( 99 ) found that paeoniflorin significantly down-regulated E-selectin expression at the gene and protein levels. Paeoniflorin also inhibited the phosphorylation of JNK and p38 in a dose dependent manner, thereby suppressed the MAPK signaling pathway.…”