Ginsenoside Rb1 inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human endothelial cells.

College of Life Sciences, Zhejiang University, Hangzhou, China.
Biological & Pharmaceutical Bulletin (Impact Factor: 1.85). 11/2008; 31(11):2050-6.
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Shengmai injection, consisting of Panax ginseng, Radix ophiopogonis and Schisandra chinensis, is a widely used Chinese medicine for the treatment of various cardiovascular diseases. In this study, tissue distribution and excretion of its multiple active components including protopanaxatriol-type (Ppt-type) ginsenosides (ginsenoside Rg1, Re, Rf and Rg2), protopanaxadiol-type (Ppd-type) ginsenosides (ginsenoside Rb1, Rd and Rc), ophiopogonin (ophiopogonin D), and lignan (schisandrin, schisandrol B and schizandrin B) in rat after single intravenous administration of Shengmai injection were reported. Ppt-type ginsenosides exhibited quick and wide distribution from blood into tissues and were eliminated rapidly through biliary, urinary and fecal excretions. Ppd-type ginsenosides Rb1, Rd and Rc distributed quickly from blood to all tissues but exhibited slow elimination by biliary and urinary excretions. Ophiopogonin D was excreted into bile with no urinary and fecal excretion, indicating its elimination in the form of secondary metabolites. Schisandrin, schisandrol B and schizandrin B was found to distribute quickly from blood into most tissues and had accumulation in these tissues. Very low biliary, urinary and fecal excretion implied that lignan was mainly excreted in the form of their metabolites. This study produced a first hand in vivo tissue distribution and dynamic profiles of the active components of Shengmai injection, providing valuable information for drug development and clinical application of Shengmai injection.
    Archives of Pharmacal Research 04/2014; · 1.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vascular inflammatory responses are key mediators of endothelial dysfunction that leads to various pathologies in many diseases including atherosclerosis and cancer. The purpose of the study was to investigate the effects and molecular mechanisms of Malvidin, a natural pigment with strong antioxidant activity, on regulating inflammatory response in endothelial cells. Our results showed that tumor necrosis factor-alpha (TNF-α) significantly increased the protein or mRNA levels of monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), whereas pretreatment with Malvidin inhibited TNF-α-induced increases of MCP-1, ICAM-1, and VCAM-1 production in a concentration-dependent manner. In addition, Malvidin could inhibit degradation of IκBα and the nuclear translocation of p65, which suggesting the anti-inflammation mechanism of Malvidin by the nuclear factor kappa B (NF-κB) pathway. These results indicate the potential role of Malvidin in preventing chronic inflammation in many diseases.
    European journal of pharmacology 12/2013; · 2.59 Impact Factor
  • Source
    [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 01/2014; 2014:748964. · 3.88 Impact Factor