Cynandione�A inhibits lipopolysaccharide-induced cell adhesion via suppression of the protein expression of VCAM‑1 in human endothelial cells

Abstract

Cynandione A (CA) is one of the most active compounds in the roots of Cynanchum wilfordii, the extracts of which have been used extensively in East Asia to treat various diseases including anti‑ischemic stroke. In the present study, the anti‑adherent activity of CA in lipopolysaccharide (LPS)‑stimulated human umbilical vascular endothelial cells (HUVECs) was investigated. CA markedly reduced the expression of vascular adhesion molecule‑1 (VCAM‑1) by LPS in HUVECs. The results also demonstrated that CA significantly reduced the expression of pro‑inflammatory and chemoattractant cytokines, including interleukin (IL)‑1β, IL‑6, IL‑8, monocyte chemoattractant protein‑1 and tumor necrosis factor‑α, in LPS‑activated human endothelial cells. CA inhibited the phosphorylation of mitogen‑activated protein kinases, including the extracellular signal‑regulated kinase 1/2 and p38 kinases. It was found that CA decreased the IKK/IκB‑α phosphorylation of inhibitor of nuclear factor (NF)‑κB kinase/inhibitor of NF‑κB‑α, suppressed translocation of the NF‑κB p65 subunit into the nucleus and inhibited the transcriptional activity of NF‑κB. CA also decreased human monocyte cell adhesion to endothelial cells in LPS‑stimulated conditions. These results demonstrated that CA inhibited the protein expression of VCAM‑1 and pro‑inflammatory cytokines by suppressing the transcriptional activity of NF‑κB. The results also suggested that CA may be important in the development of anti‑inflammatory drugs by inhibiting the expression of cell adhesion molecules.

Blocking the REDD1/TXNIP axis ameliorates LPS-induced vascular endothelial cell injury through repressing oxidative stress and apoptosis

“…IL-6, TNF-␣, and IL-1␤ are crucial inflammatory factors in the initiation and progression of cardiovascular diseases. Additionally, expression of endothelial adhesion molecules, which is induced by proinflammatory cytokines, plays an important role in vascular endothelial cell injury and leads to vascular disease (17). In the present study, we observed that LPS stimulation dramatically elevated the secretion of several proinflammatory cytokines such as IL-6, TNF-␣, IL-1␤, and MCP-1.…”

MicroRNA-126-3p Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Disruption by Regulating VCAM-1 Expression

“…Eventually the leukocytes break through the endothelial barrier and reach lesion site. Under normal physiological conditions, endothelial cells are inactive and do not express adhesion molecules, but under pathological conditions (such as BBB damage), a large number of exogenous cytokines are generated and the endothelial cells are activated, so that VCAM-1 is expressed (Park et al, 2018). VCAM-1 on the surface of endothelial cells mediates leukocyte adhesion through its interaction with VLA-4, which consists of CD49d (α4) and CD29 (β1).…”

Cynanchum wilfordii Etanolic Extract Controls Blood Cholesterol: A Double-blind, Randomized, Placebo-Controlled, Parallel Trial

“…The ethanolic extract of CW increases blood HDL-C levels and reduces the atherogenic index although there was no significant difference in total cholesterol in the high-cholesterol diet SD rats and apoE −/− mice [23]. In this study, CW was standardized with cynandione A which was reported to have anti-inflammatory effects by inhibiting VCAM-1 in human endothelial cells or inhibiting MAPK and NF-κB in macrophages [17,18]. Besides cynandione A, CW has been identified to have various phytochemicals such as dihydroxyacetophenone, acetovanillone, conduritol F, geniposide, bungeiside A and β-sitosterol [15,39].…”

“…Cynandione A has been reported to prevent ischemic stroke by regulating the pathway associated with thrombotic or embolic occlusion [16]. Cynandione A also exhibits anti-inflammatory effects by inhibiting VCAM-1 in human endothelial cells or inhibiting MAPK and NF-κB in macrophages [17,18]. Caudatin isolated from CW also exhibits antifungal activity [19].…”