This Is MS Multiple Sclerosis Community: Knowledge & Support

1: Acta Pharmacol Sin. 2001 Sep;22(9):857-60.Links
Effect of quercetin on adhesion of platelets to microvascular endothelial cells in vitro.Fan PS, Gu ZL, Liang ZQ.
Department of Pharmacology, Suzhou University, Suzhou Institute of Chinese Materia Medica, Suzhou 215007, China.

AIM: To study the effect of quercetin(Que) on the adhesion of platelets to microvascular endothelial cells (MVEC) isolated from human skin. METHODS: [3H]-adenine-labeled platelets were incubated with MVEC. Effect of Que on platelet endothelial cell adhesion molecular (PECAM) expression on MVEC was also evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: Adhesion of platelet to MVEC reached to maximum at about 30 min. Que inhibited the adhesion of platelets to MVEC in a concentration-dependent manner. Que 5 micromol/L did not show any significant inhibition. When the concentration of Que increased to 10, 20, and 40 micromol/L, the inhibition rate increased to 10.5 %, 20.0 %, and 42.2 %, respectively. Pre-incubation of Que (10 - 40 micromol/L) with labeled platelets for 30 min also inhibited the adhesion but Que 5 micromol/L did not. The inhibition rate of Que 10, 20, and 40 micromol/L was 18.2 %, 29.8 %, and 65.3 % respectively. Expression of PECAM on the endothelial cells was decreased in a concentration-dependent manner when MVEC were treated with Que (10 - 40 micromol/L) for 12 h but Que 5 micromol/L did not significantly affect the expression. CONCLUSION: Que could inhibit the adhesion of platelets to MVEC. This effect may be related to decreased expression of PECAM on MVEC.

PMID: 11749871 [PubMed - indexed for MEDLINE]

1: Cardiovasc Res. 2008 Sep 3. [Epub ahead of print] Links
Cilostazol inhibits cytokine-induced nuclear factor-{kappa}B activation via AMP-activated protein kinase activation in vascular endothelial cells.Hattori Y, Suzuki K, Tomizawa A, Hirama N, Okayasu T, Hattori S, Satoh H, Akimoto K, Kasai K.
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan.

AIMS: Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cyclic AMP (cAMP) levels and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. We hypothesized that cilostazol may prevent inflammatory cytokine induced-nuclear factor (NF)-kappaB activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells. METHODS AND RESULTS: Cilostazol was observed to activate AMPK and its downstream target, acetyl-CoA carboxylase, in human umbilical vein endothelial cells (HUVEC). Phosphorylation of AMPK with cilostazol was not affected by co-treatment with an adenylate cyclase inhibitor, SQ 22536, and a cell-permeable cAMP analogue, pCTP-cAMP, did not induce AMPK phosphorylation and had no effect on cilostazol-induced AMPK phosphorylation, suggesting that cilostazol-induced AMPK activation occurs through a signalling pathway independent of cyclic AMP. Cilostazol also dose-dependently inhibited tumour necrosis factor alpha (TNFalpha)-induced NF-kappaB activation and TNFalpha-induced IkappaB kinase activity. Furthermore, cilostazol attenuated the TNFalpha-induced gene expression of various pro-inflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 (MCP-1), and PECAM-1 in HUVEC. RNA interference of AMPKalpha1 or the AMPK inhibitor compound C attenuated cilostazol-induced inhibition of NF-kappaB activation by TNFalpha. CONCLUSION: In the light of these findings, we suggest that cilostazol might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-kappaB following AMPK activation.

PMID: 18703532 [PubMed - as supplied by publisher]

Cilostazol (pronounced /sɨˈlɒstəzɒl/) is a medication used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. It is manufactured by Otsuka Pharmaceutical Co. under the trade name Pletal.

Although drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure, studies of significant size have not addressed people without the disease.

Cilostazol is a selective cAMP phosphodiesterase inhibitor. It inhibits platelet aggregation and is a direct arterial vasodilator. Its main effects are dilation of the arteries supplying blood to the legs and decreasing platelet coagulation.

1: Diabetes Metab Res Rev. 2004 May-Jun;20(3):232-8. Links
The antidiabetic agent, gliclazide, reduces high insulin-enhanced neutrophil-transendothelial migration through direct effects on the endothelium.Okouchi M, Okayama N, Omi H, Imaeda K, Fukutomi T, Nakamura A, Itoh M.
Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. okochi@med.nagoya-cu.ac.jp

BACKGROUND AND AIM: Many lines of evidence indicate that hyperinsulinemia might be associated with coronary atherosclerosis, and, currently, there are no effective strategies for preventing this. We previously reported that high insulin enhances neutrophil-transendothelial migration, a process that involves increased surface presentation of platelet endothelial cell adhesion molecule-1 (PECAM-1) through a mitogen-activated protein (MAP) kinase-dependent event. In this current study, we examined if antidiabetic agents, especially K(ATP) channel blockers, might similarly protect against the leukocyte-endothelial cell interactions enhanced by high insulin. METHODS: Neutrophils transmigration across umbilical vein endothelial cells (in high insulin medium) with or without K(ATP) channel blockers was performed. Neutrophil migration was quantified by measuring myeloperoxidase, and surface expression of endothelial PECAM-1 was examined using cell-surface enzyme immunoassay. RESULTS: Neutrophil-transendothelial migration and PECAM-1 expression were enhanced by insulin (100 micro U/mL, 24 h) and were attenuated by gliclazide (20 micro M), but not by other K(ATP) channel blockers (glibenclamide, nateglinide, and glimepiride). Neutrophil migration and PECAM-1 expression were also increased by the mitogen-activated protein (MAP) kinase activator, anisomycin (1 micro M), and also attenuated by gliclazide. Nitric oxide (NO) synthase inhibitors did not modify either gliclazide effect. CONCLUSIONS: Our results suggest that the K(ATP) channel blocker, gliclazide, blocks high insulin-mediated neutrophil migration and PECAM-1 expression. These gliclazide effects may be mediated through the inhibition of MAP kinase activation and are unrelated to NO production. Copyright 2004 John Wiley & Sons, Ltd.

PMID: 15133755 [PubMed - indexed for MEDLINE]

Related ArticlesProtective actions of gliclazide on high insulin-enhanced neutrophil-endothelial cell interactions through inhibition of mitogen activated protein kinase and protein kinase C pathways. [Microvasc Res. 2004] High insulin enhances neutrophil transendothelial migration through increasing surface expression of platelet endothelial cell adhesion molecule-1 via activation of mitogen activated protein kinase. [Diabetologia. 2002] Participation of high glucose concentrations in neutrophil adhesion and surface expression of adhesion molecules on cultured human endothelial cells: effect of antidiabetic medicines. [J Diabetes Complications. 2002] The mechanisms of inhibitory actions of gliclazide on neutrophils-endothelial cells adhesion and surface expression of endothelial adhesion molecules mediated by a high glucose concentration. [J Diabetes Complications. 2003] Cerivastatin ameliorates high insulin-enhanced neutrophil-endothelial cell adhesion and endothelial intercellular adhesion molecule-1 expression by inhibiting mitogen-activated protein kinase activation. [J Diabetes Complications. 2003] » See all Related Articles...

1: Planta Med. 2008 Oct 20. [Epub ahead of print]
Anti-Oxidant, Anti-Inflammatory and Anti-Allergic Activities of Luteolin.Seelinger G, Merfort I, Schempp CM.
Medical Services Dr. Seelinger, Berlin, Germany.

Luteolin is a flavone which occurs in medicinal plants as well as in some vegetables and spices. It is a natural anti-oxidant with less pro-oxidant potential than the flavonol quercetin, the best studied flavonoid, but apparently with a better safety profile. It displays excellent radical scavenging and cytoprotective properties, especially when tested in complex biological systems where it can interact with other anti-oxidants like vitamins. Luteolin displays specific anti-inflammatory effects at micromolar concentrations which are only partly explained by its anti-oxidant capacities. The anti-inflammatory activity includes activation of anti-oxidative enzymes, suppression of the NFkappaB pathway and inhibition of pro-inflammatory substances. IN VIVO, luteolin reduced increased vascular permeability and was effective in animal models of inflammation after parenteral and oral application. Although luteolin is only a minor component in our nutrition (less than 1 mg/day) epidemiological studies indicate that it has the potential to protect from diseases associated with inflammatory processes such as cardiovascular disease. Luteolin often occurs in the form of glycosides in plants, but these are cleaved and the aglycones are conjugated and metabolized after nutritional uptake which has to be considered when evaluating IN VITRO studies. Some data for oral and topical bioavailability exist, but more quantitative research in this field is needed to evaluate the physiological and therapeutical potential of luteolin. Akt:serine/threonin protein kinase B COX-2:cyclooxygenase-2 CVD:cardiovascular disease DPPH:2,2-diphenyl-1-picrylhydrazyl EAE:experimental autoimmune encephalomyelitis EGCG:epigallocatechin 3-gallate fMLP:fMetLeuPhe, formyl peptide GSH:glutathione IFN-gamma:interferon gamma IkappaB:Inhibitor of kappa B IL:interleukin iNOS:inducible nitric oxygen synthase IP-10:inducible nitric oxygen synthase IRF:interferon regulatory factor LPS:lipopolysaccharide LysoPAF AcTF:1-lysophospholipide acetyltransferase MAPK:mitogen-activated protein kinase M-CSF:macrophage colony-stimulating factor NFkappaB:nuclear factor kappa B HdG:8-hydroxy-2'-deoxyguanosine PGE (2):prostaglandin E (2)PMA:phorbol myristate acetate ROS:reactive oxygen species TEAC:trolox equivalent anti-oxidant capacity TNF-alpha:tumor necrosis factor-alpha.

PMID: 18937165 [PubMed - as supplied by publisher]

AC, I saw this abstract about endothelial cells and neuronal precursor cells and I think it gives more support to what you're saying about the endothelium. It looks to me like stem cell treatment for MS might be moving towards implanting some kind of neuronal precursor cells.

but I'll put together a reference in pdf form with sources and pm you when it's ready.

1: Clin Hemorheol Microcirc. 1997 Sep-Oct;17(5):385-8. Links
Antipermeability effects of Cyclo 3 Fort in hamsters with moderate diabetes.Svensjö E, Bouskela E, Cyrino FZ, Bougaret S.
Laboratório de Pesquisas em Microcirculação, State University of Rio de Janeiro, Brazil.

Ruscus aculeatus extract (the active principle of Cyclo 3 Fort) is used to increase venous tone in patients with venous disease. In these experiments, the effects of oral Cyclo 3 Fort on capillary permeability were studied in hamsters with moderate diabetes induced by two intraperitoneal injections of streptozotocin (40 mg/kg). Hamsters were treated with a placebo or Cyclo 3 Fort, 2, 10 or 50 mg/kg/day, for 4 weeks starting 3 days after induction of diabetes. Intravital microscopy of cheek pouch preparations was performed using fluorescein-labelled dextran (FITC-dextran) as a marker for plasma exudation (leak formation). Plasma levels of glucose were measured prior to experiments. Following preparation for intravital microscopy, each cheek pouch was subjected to two applications of histamine, 5 x 10(-6) M for 5 min at 30-minute intervals. Plasma exudation (number of leaks/cm2) was significantly reduced in animals receiving Cyclo 3 Fort at doses of 10 mg/kg or above. The mean number of leaks was 258 +/- 17 in the placebo group, compared with 253 +/- 12, 125 +/- 7 (p < 0.01) and 99 +/- 7 (p < 0.01) in animals receiving Cyclo 3 Fort, 2, 10 or 50 mg/kg, respectively. Blood glucose levels did not differ between groups. Thus, oral Cyclo 3 Fort inhibited histamine-induced plasma exudation in hamsters with mild diabetes without affecting the glycaemia.

PMID: 9502536 [PubMed - indexed for MEDLINE]