Inhibitory activity of unsaturated fatty acids and anacardic acids toward soluble tissue factor-factor VIIa complex

Area of Science:

• Phytochemistry
• Pharmacology
• Biochemistry

Background:

• Traditional Chinese medicine utilizes plants like Salvia miltiorrhiza and Ginkgo biloba for cardiovascular and cerebrovascular diseases.
• The soluble tissue factor/activated factor VII complex (sTF/VIIa) plays a crucial role in the blood coagulation cascade.

Purpose of the Study:

• To identify and characterize compounds from traditional Chinese medicinal plants that inhibit sTF/VIIa amidolytic activity.
• To elucidate the structure-activity relationships of fatty acids and anacardic acids for sTF/VIIa inhibition.

Main Methods:

• Isolation and purification of five inhibitory compounds from Salvia miltiorrhiza and Ginkgo biloba.
• Determination of IC50 values for the isolated compounds.
• Structure-activity relationship studies involving various fatty acids and anacardic acids.
• Preincubation studies to investigate the mechanism of inhibition.

Main Results:

• Linolenic, linoleic, and oleic acids from Salvia miltiorrhiza, and two anacardic acids from Ginkgo biloba inhibited sTF/VIIa with IC50 values between 30-80 micromol/L.
• Palmitic acid and a marine sponge compound did not show inhibitory activity.
• Fatty acids with at least one cis double bond were essential for activity, with two or three cis double bonds being optimal.
• Preincubation studies suggested that these fatty acids bind to VIIa, preventing sTF binding.

Conclusions:

• Specific fatty acids and anacardic acids isolated from traditional Chinese medicinal plants possess inhibitory activity against sTF/VIIa.
• The presence and number of cis double bonds in fatty acids are critical for their inhibitory potency.
• These findings suggest a potential mechanism for the use of these plants in treating cardiovascular and cerebrovascular diseases, possibly through modulation of the coagulation cascade.