We investigated whether ginsenoside Rb1 (Rb1) could block tumor necrosis factor-alpha (TNF-alpha)-induced over-expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and human lung microvascular endothelial cells (HMVECs-L). Cells were treated with various concentrations of TNF-alpha with or without Rb1 pre-treatment for 16 h. The mRNA and protein levels of VCAM-1 were determined with real-time polymerase chain reaction (PCR) and flow cytometry, respectively. Human monocytic THP-1 cells labeled with fluorescent dye (Calcein-AM) was used for the adhesion assay on HUVEC monolayers. Dihydroethidium (DHE) was used to demonstrate in situ levels of superoxide production. JC-1 dye was used to measure changes in mitochondrial membrane potential. Activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) was determined by Bio-Plex immunoassay. TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%, respectively (p<0.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal-regulated kinase 1/2 and IkappaBalpha. In conclusion, Rb1 effectively blocked the TNF-alpha-induced over-expression of VCAM-1, increased THP-1 adhesion and over-production of superoxide anion. Furthermore, Rb1 inhibited TNF-alpha-induced MAPKs and NF-kappaB activation. These data suggested that Rb1 might have potential therapeutic effects in controlling inflammation in vascular diseases.
"The impact of TNF-α on monocyte adhesion to the endothelium is well known: TNF-α stimulation of endothelial cells leads to an activation of NFκB followed by a transcriptional activation of several adhesion molecules, like VCAM-1, ICAM-1 and E-Selectin  . Besides the transcriptional activation of adhesion molecules, TNF-α is able to induce cytoskeletal changes leading to the clustering of adhesion receptors on the surface of endothelial cells , which demonstrates the multifunctional influence of TNF-α on monocyte adhesion. "
[Show abstract][Hide abstract] ABSTRACT: The ligand ephrin Al is more often discussed to play a role in the development of the atherosclerotic plaque and in this context especially in the monocyte adhesion to endothelial cells. As tumor necrosis factor-alpha (TNF-alpha) is known to induce monocyte adhesion to endothelium and ephrin A1 expression, the present study focuses on the involvement of ephrin A1 in TNF-alpha-mediated monocyte adhesion. The analysis of different members of the Eph/ephrin system in TNF-alpha-treated human umbilical vein endothelial cells (HUVEC) revealed that especially ephrinAl was found to be highly regulated by TNF-alpha compared to other members of the Eph family. This effect is also present in arterial endothelial cells from the umbilical artery and from the coronary artery. This regulation is dependent on NF kappa B-activation as shown by the expression of a constitutive-active I kappa B-mutant By using siRNA-mediated silencing and adenoviral overexpression of ephrinA1 in HUVEC, the involvement of ephrinA1 in the TNF-alpha triggered monocyte adhesion to endothelial cells could be demonstrated. In addition, these results could be verified by quantitative adhesion measurement using atomic force microscopy-based single-cell force spectroscopy and under flow conditions. Furthermore, this effect is mediated via the EphA4 receptor. EphrinA1 does not influence the mRNA or protein expression of the adhesion receptors VCAM-1 and ICAM-1 in endothelial cells. However, the surface presentation of these adhesion receptors is modulated in an ephrinA1-dependent manner. In conclusion, these data demonstrate that ephrinA1 plays an important role in the TNF-alpha-mediated adhesion of monocytes to endothelial cells, which might be of great importance in the context of atherosclerosis.
Journal of Molecular and Cellular Cardiology 10/2014; 77. DOI:10.1016/j.yjmcc.2014.10.010 · 4.66 Impact Factor
"Saponin components of ginsenosides are divided into two different structural classes: the 20(S)-protopanaxadiol (PD) group of ginsenosides including Ra1, Ra2, Ra3, Rb1, Rb2, Rb3, Rc, Rd, Rg3, and Rh2 and 20(S)-protopanaxatriol (PT) group ginsenosides such as Re, Rf, Rg1, Rg2, and Rh1 . PD ginsenosides including Rb1 , Rd , Rg3 , and Rh2  and PT ginsenosides such as Rg1   and Rh1  have been reported to exhibit both in vivo and in vitro antiinflammatory properties in different studies related to inflammation . Individual ginsenoside, however, due to incomplete pharmacokinetic parameters and unknown toxicities, has rarely been reported for the clinical study so far . "
[Show abstract][Hide abstract] ABSTRACT: Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previous in vitro data displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3(+)/CD69(+), CD4(+)/CD25(+), CD8(+) T-cell, CD19(+), B220/CD23(+) B-cell, MHCII(+)/CD11c(+), and Gr-1(+)/CD11b(+) cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF- α , IL-1 β , IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.
Mediators of Inflammation 04/2014; 2014(2):748964. DOI:10.1155/2014/748964 · 3.24 Impact Factor
"DT-13 attenuates serum withdrawal-induced mitochondrial dysfunction The mitochondrion is an important organelle for the production of cellular energy and has key role in programmed cell death. The maintenance of membrane potential is essential for mitochondrial integrity and bioenergetic functions  "
[Show abstract][Hide abstract] ABSTRACT: Dwarf lilyturf tuber is widely used in clinics to prevent cardiovascular diseases. DT -13, the saponin monomer 13 of dwarf lilyturf tuber, shows protective activities in anti-thrombosis, anti-inflammation, and cardioprotective. However, little is known about the cellular function of DT-13 in cardiovascular system. Vascular endothelial cells (EC) are important to maintain the integrity of the vasculature throughout entire body. Dysregulation of EC may lead to pathophysiological processes of numerous cardiovascular diseases. We thus tested the function of DT-13 in EC. In the present study, we are the first to report that DT-13 has anti-apoptosis activity on human umbilical vein endothelial cells (HUVEC), potentially through down regulation of cleaved caspase-3 and cleaved PARP expression. DT-13 also increased mitochondrial membrane potential. To explore the potential mechanism, we investigated the effect of DT-13 on Akt and MAPK pathways and found that DT-13 was involved in Akt signaling confirmed by using PI3K/Akt inhibitor LY294002. Thus, DT-13 could improve survival of EC and therefore be a potential clinical use in the treatment of cardiovascular diseases.
Biochemical and Biophysical Research Communications 11/2013; 443(1). DOI:10.1016/j.bbrc.2013.11.056 · 2.30 Impact Factor
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