Authors:
Mai MorishitaFaculty of Nutrition, Kobe Gakuin University, Kobe, Japan

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Aki NaemuraFaculty of Nutrition, Kobe Gakuin University, Kobe, Japan

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Yukinori TamuraDepartments of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

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Hideaki YamayaPomology Division of Apple Experiment Station, Aomori Agriculture and Forestry Research Center, Aomori, Japan

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Yuko TsudaFaculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan

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Yoshio OkadaFaculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan

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Kiyotaka OkadaFaculty of Medicine, Kinki University, Osakasayama, Japan

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Osamu MatsuoFaculty of Medicine, Kinki University, Osakasayama, Japan

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Junichiro YamamotoFaculty of Nutrition, Kobe Gakuin University, Kobe, Japan

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Abstract

Prevention of arterial thrombotic diseases has high priority in developed countries. As inappropriate diet is known to enhance the risk for acute thrombotic events, a regular diet with experimentally proven antithrombotic effect might be a beneficial way of prevention. The present study is part of a series of investigations testing fruits and vegetables for antithrombotic activity. The Global Thrombosis Test was used to screen sixteen different apple varieties for antiplatelet and thrombolytic activities. The in vitro effective varieties were further investigated using the laser-induced thrombosis model in mice. In order to investigate the mechanism, hemostatometry and flow-mediated vasodilation test (FMV) were performed. Apple varieties were grouped into subclasses according to their antithrombotic activity. AP-2, AP-13, AP-14 and AP-15 showed significant antithrombotic effect both in vitro and in vivo. AP-8 was antithrombotic in vitro but could not determine in vivo because of the shortage of the sample. The antithrombotic effect was mainly due to activation of endogenous thrombolytic mechanism. The mechanism of such enhanced thrombolysis was investigated using a synthetic inhibitor highly specific to plasmin, polyclonal IgG to t-PA and u-PA, and testing the antithrombotic effect in t-PA knockout mice. Antithrombotic activity was prevented by the synthetic plasmin inhibitor and IgG against t-PA but not against u-PA. There was no antithrombotic activity in t-PA knockout mice. Intake of antithrombotic apple filtrate did not affect FMV and platelet reactivity. The antithrombotic effect was heat stable at 100 °C for 10 min. These results suggest that the mechanism of antithrombotic activity involves an increased t-PA release from the vascular endothelium and an inhibition of plasminogen activator inhibitor (PAI-1) release from activated platelets. The present findings justify including antithrombotic apple varieties in an antithrombotic diet.

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2019  
Scimago
H-index
11
Scimago
Journal Rank
0,220
Scimago
Quartile Score
Medicine (miscellaneous) Q3
Scopus
Cite Score
155/133=1,2
Scopus
Cite Score Rank
General Medicine 199/529 (Q2)
Scopus
SNIP
0,343
Scopus
Cites
206
Scopus
Documents
23

 

Interventional Medicine and Applied Science
Language English
Size  
Year of
Foundation
2009
Publication
Programme
changed title
Volumes
per Year
 
Issues
per Year
 
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2061-1617 (Print)
ISSN 2061-5094 (Online)

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