TY - JOUR

T1 - Antiplatelet Effect of Nobiletin is Mediated by Activation of A2A Adenosine Receptor

AU - Shpakova, V. S.

AU - Avdeeva, A. V.

AU - Al Arawe, N.

AU - Prilepskaya, A. M.

AU - Gambaryan, S. P.

AU - Alekseeva, E. S.

AU - Rukoyatkina, N. I.

PY - 2021/12/14

Y1 - 2021/12/14

N2 - Nobiletin is a polymethoxylated flavone derived from citrus peels that possesses a wide range of beneficial effects. Specifically, nobiletin exhibits anti-inflammatory, antibacterial, and antioxidant effects. Recent research showed that nobiletin is able to diminish platelet adhesion and aggregation, indicating this compound as a potential therapeutic drug in thrombosis therapy. However, the exact mechanism of nobiletin action on platelets is unclear. Hence, the main goal of our study was to investigate the molecular mechanism of nobiletin-induced platelet inhibition. We demonstrated that nobiletin blocks induced platelet activation and does not cause platelet apoptosis. Inhibition effect of nobiletin on platelets is at least partly mediated by activation of A(2A) adenosine receptor and consequent AC/cAMP/PKA signaling pathway activation.

AB - Nobiletin is a polymethoxylated flavone derived from citrus peels that possesses a wide range of beneficial effects. Specifically, nobiletin exhibits anti-inflammatory, antibacterial, and antioxidant effects. Recent research showed that nobiletin is able to diminish platelet adhesion and aggregation, indicating this compound as a potential therapeutic drug in thrombosis therapy. However, the exact mechanism of nobiletin action on platelets is unclear. Hence, the main goal of our study was to investigate the molecular mechanism of nobiletin-induced platelet inhibition. We demonstrated that nobiletin blocks induced platelet activation and does not cause platelet apoptosis. Inhibition effect of nobiletin on platelets is at least partly mediated by activation of A(2A) adenosine receptor and consequent AC/cAMP/PKA signaling pathway activation.

KW - platelets

KW - nobiletin

KW - antiplatelet therapy

KW - cyclic adenosine monophosphate (cAMP)

KW - cyclic guanosine monophosphate (cGMP)

KW - PKA

KW - PKG

KW - adenosine receptor

KW - VASODILATOR-STIMULATED PHOSPHOPROTEIN

KW - NITRIC-OXIDE

KW - L-ARGININE

KW - IN-VITRO

KW - PLATELETS

KW - THROMBOSIS

KW - MODULATION

KW - MECHANISM

KW - APOPTOSIS

U2 - 10.1134/S1990747821060106

DO - 10.1134/S1990747821060106

M3 - статья

VL - 15

SP - 387

EP - 394

JO - Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology

JF - Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology

SN - 1990-7478

IS - 4

ER -