rosmarinic-acid and Hemorrhage

In our previous paper, we reported that rosmarinic acid (1) of Argusia argentea could neutralize snake venom induced hemorrhagic action. Rosmarinic acid (1) consists of two phenylpropanoids: caffeic acid (2) and 3-(3,4-dihydroxyphenyl)lactic acid (3). In this study, we investigated the structural requirements necessary for inhibition of snake venom activity through the use of compounds, which are structurally related to rosmarinic acid (1). By examining anti-hemorrhagic activity of cinnamic acid analogs against Protobothrops flavoviridis (Habu) venom, it was revealed that the presence of the E-enoic acid moiety (-CH=CH-COOH) was critical. Furthermore, among the compound tested, it was concluded that rosmarinic acid (1) (IC(50) 0.15 μM) was the most potent inhibitor against the venom.

Topics: Animals; Antivenins; Caffeic Acids; Cinnamates; Crotalid Venoms; Depsides; Hemorrhage; Humans; Male; Mice; Rosmarinic Acid; Snakes; Structure-Activity Relationship

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.

Topics: Animals; Antivenins; Boraginaceae; Cinnamates; Depsides; Dose-Response Relationship, Drug; Hemorrhage; Mice; Plant Extracts; Plant Leaves; Plant Stems; Rosmarinic Acid; Snake Venoms

In our previous report, rosmarinic acid (RA) was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae). The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu). This article presents mechanistic evidence of RA's neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability.

Topics: Animals; Antivenins; Boraginaceae; Cell Survival; Cinnamates; Collagen Type IV; Depsides; Drug Stability; Edema; Fibrinogen; Hemorrhage; Hot Temperature; Human Umbilical Vein Endothelial Cells; Humans; Hydrolysis; Mice; Muscle, Skeletal; Phytotherapy; Plant Extracts; Rosmarinic Acid; Viper Venoms; Viperidae