The garlic-derived organosulfur compound diallyl trisulphide suppresses tissue factor function

Area of Science:

• Biochemistry
• Pharmacology
• Cardiovascular Research

Background:

• Tissue factor (TF) initiates extrinsic coagulation and is implicated in thromboembolism.
• Diallyl trisulphide (DATS), a garlic-derived compound, possesses diverse pharmacological properties.
• Understanding DATS's impact on TF-mediated coagulation and atherosclerosis is crucial for therapeutic development.

Purpose of the Study:

• To investigate the inhibitory effect of DATS on TF-driven extrinsic coagulation.
• To determine if DATS modulates TF expression in endothelial cells.
• To evaluate the potential of DATS in mitigating atherosclerosis and associated thromboembolism.

Main Methods:

• TF activity was quantified using a clotting assay in TF-expressing HL60 cells.
• TF mRNA and protein levels were assessed via real-time PCR and Western blotting in TNF-α-stimulated HUVECs.
• Apolipoprotein E-deficient mice were used to assess the in vivo effects of DATS on arteriosclerosis.

Main Results:

• DATS demonstrated dose-dependent inhibition of TF activity.
• DATS significantly reduced TNF-α-induced TF mRNA and protein expression by inhibiting JNK signaling.
• DATS administration in mice showed a trend towards decreased atherosclerotic lesion size.

Conclusions:

• DATS effectively inhibits TF activity and expression, offering a potential therapeutic strategy against TF-driven coagulation.
• DATS exhibits anti-atherosclerotic properties, suggesting a dual role in preventing plaque formation and TF function.
• These findings highlight DATS as a promising agent for managing thromboembolism associated with atherosclerosis.