Pharmacological actions of nobiletin in the modulation of platelet function

Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517, Roweth, H., Ali, M., Unsworth, A., Stainer, A., Flora, G., Crescente, M., Jones, C. ORCID: https://orcid.org/0000-0001-7537-1509, Moraes, L. and Gibbins, J. ORCID: https://orcid.org/0000-0002-0372-5352 (2015) Pharmacological actions of nobiletin in the modulation of platelet function. British Journal of Pharmacology, 172 (16). pp. 4133-4145. ISSN 0007-1188 doi: 10.1111/bph.13191

Abstract/Summary

Background and Purpose The discovery that flavonoids are capable of inhibiting platelet function has led to their investigation as potential antithrombotic agents. However, despite the range of studies on the antiplatelet properties of flavonoids, little is known about the mechanisms by which flavonoids inhibit platelet function. In this study, we aimed to explore the pharmacological effects of a polymethoxy flavonoid, nobiletin in the modulation of platelet function. Experimental Approach The ability of nobiletin to modulate platelet function was explored by using a range of in vitro and in vivo experimental approaches. Aggregation, dense granule secretion and spreading assays were performed using washed platelets. The fibrinogen binding, α-granule secretion and calcium mobilisation assays were performed using platelet-rich plasma and whole blood was used in impedance aggregometry and thrombus formation experiments. The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice. Key Results Nobiletin was shown to supress a range of well-established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilisation and thrombus formation. Nobiletin was shown to extend bleeding time in mice and reduce the phosphorylation of Akt and PLCγ2 within the collagen receptor (GPVI) - stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of VASP, a protein whose activity is associated with inhibitory cyclic nucleotide signalling. Conclusions and Implications This study provides insight into the underlying molecular mechanisms through which nobiletin modulates haemostasis and thrombus formation. Therefore nobiletin may represent a potential antithrombotic agent of dietary origins.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/40276
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Uncontrolled Keywords	Platelets; thrombosis; haemostasis; nobiletin
Publisher	Wiley
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