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Pharmacological actions of nobiletin in the modulation of platelet function.

Vaiyapuri S, Roweth H, Ali MS, Unsworth AJ, Stainer AR, Flora GD, Crescente M, Jones CI, Moraes LA, Gibbins JM - Br. J. Pharmacol. (2015)

Bottom Line: The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice.Nobiletin extended bleeding time in mice and reduced the phosphorylation of PKB (Akt) and PLCγ2 within the collagen receptor (glycoprotein VI)-stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of vasodilator-stimulated phosphoprotein, a protein whose activity is associated with inhibitory cyclic nucleotide signalling.Therefore, nobiletin may represent a potential antithrombotic agent of dietary origins.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK.

No MeSH data available.


Related in: MedlinePlus

Nobiletin limits thrombus formation in vitro and extends bleeding time in mice. DiOC6 labelled human blood was pre-incubated with vehicle or different concentrations of nobiletin and perfused over collagen-coated Vena8 BioChips. Images were obtained every 30 s for up to 10 min and representative images (at 0, 2, 4, 6, 8 and 10 min) are shown in (A). The fluorescence intensity of thrombi obtained in the absence of nobiletin was taken as 100% and compared with the levels obtained with different concentrations of nobiletin (B). Data represent mean ± SD (n = 4). The P-values shown in the figure are as calculated by non-parametric repeated measures anova (Friedman test; ****P < 0.0001). The effect of nobiletin (estimated 50 μM) on haemostasis in mice was analysed by measuring the bleeding time after removal of 1 mm of tail tip. The bleeding time obtained with vehicle-treated group was compared with nobiletin-treated mice (C). Data represent mean ± SD (n = 7 mice for vehicle control or nobiletin-treated group). The significance between control and treated groups, and the P-values were calculated by Student's t-test.
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fig04: Nobiletin limits thrombus formation in vitro and extends bleeding time in mice. DiOC6 labelled human blood was pre-incubated with vehicle or different concentrations of nobiletin and perfused over collagen-coated Vena8 BioChips. Images were obtained every 30 s for up to 10 min and representative images (at 0, 2, 4, 6, 8 and 10 min) are shown in (A). The fluorescence intensity of thrombi obtained in the absence of nobiletin was taken as 100% and compared with the levels obtained with different concentrations of nobiletin (B). Data represent mean ± SD (n = 4). The P-values shown in the figure are as calculated by non-parametric repeated measures anova (Friedman test; ****P < 0.0001). The effect of nobiletin (estimated 50 μM) on haemostasis in mice was analysed by measuring the bleeding time after removal of 1 mm of tail tip. The bleeding time obtained with vehicle-treated group was compared with nobiletin-treated mice (C). Data represent mean ± SD (n = 7 mice for vehicle control or nobiletin-treated group). The significance between control and treated groups, and the P-values were calculated by Student's t-test.

Mentions: Given the dramatic effects of nobiletin on platelet function, its effects on thrombus formation were assessed in vitro in whole blood under arterial flow conditions. Fluorescently labelled (DiOC6) human blood was pre-incubated with vehicle control or different concentrations of nobiletin (12.5, 25, 50 and 100 μM) and perfused over collagen-coated Vena8 biochips for 10 min at a shear rate of 20 dynes·cm−2. Normal progression of thrombus formation was observed in vehicle-treated samples, whereas a clear reduction in thrombus volume and fluorescence intensity (Figure 4A and 4B) was observed at all concentrations of nobiletin used. These data suggest that nobiletin is able to reduce both initial platelet adhesion and subsequent thrombus formation.


Pharmacological actions of nobiletin in the modulation of platelet function.

Vaiyapuri S, Roweth H, Ali MS, Unsworth AJ, Stainer AR, Flora GD, Crescente M, Jones CI, Moraes LA, Gibbins JM - Br. J. Pharmacol. (2015)

Nobiletin limits thrombus formation in vitro and extends bleeding time in mice. DiOC6 labelled human blood was pre-incubated with vehicle or different concentrations of nobiletin and perfused over collagen-coated Vena8 BioChips. Images were obtained every 30 s for up to 10 min and representative images (at 0, 2, 4, 6, 8 and 10 min) are shown in (A). The fluorescence intensity of thrombi obtained in the absence of nobiletin was taken as 100% and compared with the levels obtained with different concentrations of nobiletin (B). Data represent mean ± SD (n = 4). The P-values shown in the figure are as calculated by non-parametric repeated measures anova (Friedman test; ****P < 0.0001). The effect of nobiletin (estimated 50 μM) on haemostasis in mice was analysed by measuring the bleeding time after removal of 1 mm of tail tip. The bleeding time obtained with vehicle-treated group was compared with nobiletin-treated mice (C). Data represent mean ± SD (n = 7 mice for vehicle control or nobiletin-treated group). The significance between control and treated groups, and the P-values were calculated by Student's t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4543618&req=5

fig04: Nobiletin limits thrombus formation in vitro and extends bleeding time in mice. DiOC6 labelled human blood was pre-incubated with vehicle or different concentrations of nobiletin and perfused over collagen-coated Vena8 BioChips. Images were obtained every 30 s for up to 10 min and representative images (at 0, 2, 4, 6, 8 and 10 min) are shown in (A). The fluorescence intensity of thrombi obtained in the absence of nobiletin was taken as 100% and compared with the levels obtained with different concentrations of nobiletin (B). Data represent mean ± SD (n = 4). The P-values shown in the figure are as calculated by non-parametric repeated measures anova (Friedman test; ****P < 0.0001). The effect of nobiletin (estimated 50 μM) on haemostasis in mice was analysed by measuring the bleeding time after removal of 1 mm of tail tip. The bleeding time obtained with vehicle-treated group was compared with nobiletin-treated mice (C). Data represent mean ± SD (n = 7 mice for vehicle control or nobiletin-treated group). The significance between control and treated groups, and the P-values were calculated by Student's t-test.
Mentions: Given the dramatic effects of nobiletin on platelet function, its effects on thrombus formation were assessed in vitro in whole blood under arterial flow conditions. Fluorescently labelled (DiOC6) human blood was pre-incubated with vehicle control or different concentrations of nobiletin (12.5, 25, 50 and 100 μM) and perfused over collagen-coated Vena8 biochips for 10 min at a shear rate of 20 dynes·cm−2. Normal progression of thrombus formation was observed in vehicle-treated samples, whereas a clear reduction in thrombus volume and fluorescence intensity (Figure 4A and 4B) was observed at all concentrations of nobiletin used. These data suggest that nobiletin is able to reduce both initial platelet adhesion and subsequent thrombus formation.

Bottom Line: The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice.Nobiletin extended bleeding time in mice and reduced the phosphorylation of PKB (Akt) and PLCγ2 within the collagen receptor (glycoprotein VI)-stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of vasodilator-stimulated phosphoprotein, a protein whose activity is associated with inhibitory cyclic nucleotide signalling.Therefore, nobiletin may represent a potential antithrombotic agent of dietary origins.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK.

No MeSH data available.


Related in: MedlinePlus