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

J Nat Prod. 1998 Nov;61(11):1352-5. doi: 10.1021/np980117p.


Five compounds, which inhibited the amidolytic activity of soluble tissue factor/activated factor VII complex (sTF/VIIa), were isolated from two traditional Chinese medicinal plants commonly used in the treatment of cardiovascular and cerebrovascular diseases. The active compounds were found to be linolenic, linoleic, and oleic acids from roots of Salvia miltiorrhiza; and two anacardic acids, 6-(8'Z-pentadecenyl)- and 6-(10'Z-heptadecenyl)-salicylic acids, from leaves of Ginkgo biloba. The IC50 values were in the range 30-80 micromol/L. Palmitic acid, isolated from roots of Salvia miltiorrhiza, and 2-[(3',7',11',15'-tetramethyl)-2'E,6'E,10'E, 14'E-hexadecatetraenyl]-1,4-hydroquinone, isolated from the marine sponge Adocia viola, did not inhibit sTF/VIIa. Further expansion of the structure-activity relationship to include anacardic acids, 6-(8'Z,11'Z-heptadecadienyl)- and 6-(8'Z, 11'Z, 14'Z-heptadecatrienyl)-salicylic acids from leaves of Anacardium spondias, and other fatty acids demonstrated that at least one cis double bond was essential for inhibitory activity, and that fatty acids containing two or three cis double bonds were optimal. Evidence from preincubation studies implied that these fatty acids may exert their effect by binding to VIIa and consequently preventing binding of sTF to VIIa.

MeSH terms

  • Anacardic Acids*
  • Enzyme Inhibitors / pharmacology*
  • Factor VIIa / antagonists & inhibitors*
  • Fatty Acids, Unsaturated / pharmacology*
  • Humans
  • Plant Extracts / chemistry
  • Plant Roots / chemistry
  • Plants, Medicinal / chemistry
  • Recombinant Proteins / chemistry
  • Salicylates / pharmacology*
  • Trypsin Inhibitors / isolation & purification
  • Trypsin Inhibitors / pharmacology


  • Anacardic Acids
  • Enzyme Inhibitors
  • Fatty Acids, Unsaturated
  • Plant Extracts
  • Recombinant Proteins
  • Salicylates
  • Trypsin Inhibitors
  • anacardic acid
  • Factor VIIa