In vitro and in vivo antithrombotic and cytotoxicity effects of ferulic acid

• Published in: Journal of biochemical and molecular toxicology Vol. 32; no. 1
• Main Authors: Choi, Jun‐Hui, Park, Jong‐Kook, Kim, Ki‐Man, Lee, Hyo‐Jeong, Kim, Seung
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018
• Subjects: 3T3-L1 Cells; Acids; Activation; AKT protein; Animals; anticoagulant; Anticoagulants - adverse effects; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; antiplatelet; Biocompatibility; Blood Platelets - drug effects; Blood Platelets - secretion; Cell lines; Cell Survival - drug effects; Clot Retraction - drug effects; Collagen; Coumaric Acids - adverse effects; Coumaric Acids - pharmacology; Coumaric Acids - therapeutic use; Cytotoxicity; Disease Models, Animal; Epinephrine; Erythrocytes; Erythrocytes - cytology; Erythrocytes - drug effects; Ferulic acid; Hemostasis - drug effects; Hep G2 Cells; Humans; Leukocytes; Leukocytes - cytology; Leukocytes - drug effects; Male; Mice; Mice, Inbred ICR; NIH 3T3 Cells; Phosphorylation; platelet activation; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Platelets; Prolongation; Secretion; Serotonin; Serotonin - chemistry; Serotonin - secretion; Serotonin Antagonists - adverse effects; Serotonin Antagonists - pharmacology; Serotonin Antagonists - therapeutic use; Therapeutic targets; Thrombin; Thromboembolism; Thromboembolism - prevention & control; Toxicity; ferulic acid; anticoagulant; antiplatelet; cytotoxicity; platelet activation
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.22004

We discovered recently in vitro and in vivo antithrombotic and cytotoxicity effects of ferulic acid. The cytotoxicity assays showed that ferulic acid (∼300 μg/mL) did not cause any significant toxicity on three cell lines, platelets, leukocytes, and erythrocytes. In vitro assays showed inhibitory effects of ferulic acid on thrombin (THR)‐ or collagen/epinephrine‐stimulated platelet activation by inhibiting platelet aggregation, and decreasing clot retraction activity. The in vitro effect of ferulic acid on THR‐stimulated platelet activation was proved by the decrease in the secretion of serotonin from the platelets. The anticoagulant effects of ferulic acid were confirmed by the prolongation of the intrinsic or/and extrinsic pathways and the delay of recalcification time in plasma coagulation. Ferulic acid had antithrombotic effect in acute thromboembolism model in vivo, and decreased the expression of αIIbβ3/FIB and phosphorylation of AKT in THR‐stimulated platelet activation in vivo, and their antithrombotic efficacies hold promise for therapeutic targeting in our ongoing studies.