Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury.
Flavonoids exhibit a variety of beneficial effects in cardiovascular diseases. Although their therapeutic properties have been attributed mainly to their antioxidant action, they have additional protective mechanisms such as inhibition of signal transducer and activator of transcription 1 (STAT1) activation. Here, we have investigated the cardioprotective mechanisms of strong antioxidant flavonoids such as quercetin, myricetin and delphinidin. Although all of them protect the heart from ischemia/reperfusion-injury, myricetin and delphinidin exert a more pronounced protective action than quercetin by their capacity to inhibit STAT1 activation. Biochemical and computer modeling analysis indicated the direct interaction between STAT1 and flavonoids with anti-STAT1 activity.
Scarabelli
Tiziano M
TM
Center for Heart and Vessel Preclinical Studies, St. John Hospital and Medical Center, Wayne State University School of Medicine, Detroit, USA.
Mariotto
Sofia
S
Abdel-Azeim
Safwat
S
Shoji
Kazuo
K
Darra
Elena
E
Stephanou
Anastasis
A
Chen-Scarabelli
Carol
C
Marechal
Jean Didier
JD
Knight
Richard
R
Ciampa
Anna
A
Saravolatz
Louis
L
de Prati
Alessandra Carcereri
AC
Yuan
Zhaokan
Z
Cavalieri
Elisabetta
E
Menegazzi
Marta
M
Latchman
David
D
Pizza
Cosimo
C
Perahia
David
D
Suzuki
Hisanori
H
D000818:Animals; D000872:Anthocyanins / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000872:Anthocyanins; D000975:Antioxidants; D005419:Flavonoids; D050794:STAT1 Transcription Factor; C040015:myricetin; C017185:delphinidin