Rosmarinic acid in Argusia argentea inhibits snake venom-induced hemorrhage

A methanolic extract of Argusia (or Messerschmidia or Tournefortia) argentea (Boraginaceae) significantly inhibited hemorrhage induced by crude venom of Trimeresurus flavoviridis. The extract was then separated according to antivenom activity by using silica gel column chromatography and HPLC equipped with an octadecylsilanized silica gel (ODS) column to afford rosmarinic acid (RA) (1) as an active principle. RA (1) significantly inhibited the hemorrhagic effect of crude venoms of T. flavoviridis, Crotalus atrox, Gloydius blomhoffii, Bitis arietans as well as snake venom metalloproteinases, HT-b (C. atrox), bilitoxin 2 (Agkistrodon bilineatus), HF (B. arietans), and Ac1-proteinase (Deinagkistrodon acutus). This is the first report of the antihemorrhage activity of RA (1), and RA (1) greatly contributes to the antihemorrhagic efficiency of A. argentea against crude snake venoms and hemorrhagic toxins.