Taxifolin Inhibits Platelet Activation and Thrombosis by Regulating the PI3K/Akt and MAPK Signaling Pathways

Area of Science:

• Biochemistry
• Pharmacology
• Cardiovascular Research

Background:

• Platelet activation is central to cardiovascular disease development.
• The antiplatelet and antithrombotic mechanisms of taxifolin are not well understood.
• Taxifolin is a natural dihydroflavonol with known antioxidant properties.

Purpose of the Study:

• To investigate the effects of taxifolin on platelet function and thrombus formation.
• To identify the molecular targets of taxifolin in platelets.
• To evaluate the therapeutic potential of taxifolin in thrombosis models.

Main Methods:

• In vitro platelet aggregation and adhesion assays using various agonists.
• Assessment of thromboxane A2 (TXA2) synthesis and integrin αIIbβ3 signaling.
• In vivo studies using pulmonary embolism and arterial thrombosis models.
• Network pharmacology and molecular docking analyses to identify targets.
• Western blot analysis to assess signaling pathway phosphorylation.

Main Results:

• Taxifolin inhibited platelet aggregation induced by multiple agonists (ADP, collagen, thrombin, U46619, convulxin).
• It reduced platelet adhesion, TXA2 synthesis, and integrin αIIbβ3 signaling.
• Taxifolin demonstrated efficacy in preventing pulmonary embolism and arterial thrombosis in vivo with no significant side effects.
• Network pharmacology identified MAPK1, AKT1, SRC, PIK3R1, and MAPK8 as potential targets.
• Molecular docking confirmed taxifolin's interaction with MAPK1, and it inhibited ERK, p38, JNK, and Akt phosphorylation.

Conclusions:

• Taxifolin exhibits significant antiplatelet and antithrombotic activities.
• Its mechanism involves the inhibition of key signaling pathways, including MAPK and PI3K/Akt.
• Taxifolin shows promise as a safe therapeutic agent for preventing cardiovascular events associated with thrombosis.