Journal article
Pharmacological actions of nobiletin in the modulation of platelet function
British journal of pharmacology, Vol.172(16), pp.4133-4145
08/2015
DOI: 10.1111/bph.13191
PMCID: PMC4543618
PMID: 25988959
Abstract
Background and PurposeThe 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 ApproachThe 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. Fibrinogen binding, -granule secretion and calcium mobilization 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 ResultsNobiletin was shown to suppress a range of well-established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilization and thrombus formation. Nobiletin extended bleeding time in mice and reduced the phosphorylation of PKB (Akt) and PLC2 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.
Conclusions and ImplicationsThis 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.
Details
- Title: Subtitle
- Pharmacological actions of nobiletin in the modulation of platelet function
- Creators
- Sakthivel Vaiyapuri - University of ReadingHarvey Roweth - University of ReadingMarfoua S. Ali - University of ReadingAmanda J. Unsworth - University of ReadingAlexander R. Stainer - University of ReadingGagan D. Flora - University of ReadingMarilena Crescente - University of ReadingChris I. Jones - University of ReadingLeonardo A. Moraes - University of ReadingJonathan M. Gibbins - University of Reading
- Resource Type
- Journal article
- Publication Details
- British journal of pharmacology, Vol.172(16), pp.4133-4145
- DOI
- 10.1111/bph.13191
- PMID
- 25988959
- PMCID
- PMC4543618
- NLM abbreviation
- Br J Pharmacol
- ISSN
- 0007-1188
- eISSN
- 1476-5381
- Publisher
- Wiley
- Number of pages
- 13
- Grant note
- PG/11/125/29320; RG/09/011/28094 / British Heart Foundation G0701399; MR/J002666/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0701399; MR/J002666/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MR/J002666/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NH/10/2/28425; FS/11/86/29137; PG/11/125/29320; RG/09/011/28094; PG/08/100/26125; PG/13/93/30593 / British Heart Foundation
- Language
- English
- Date published
- 08/2015
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984949463202771
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