Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku, Nagoya, 468-8503, Japan.
Toxins (Basel). 2010 Oct;2(10):2478-89. doi: 10.3390/toxins2102478. Epub 2010 Oct 25.
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.
在我们之前的报告中，迷迭香酸 (RA) 被发现是 Argusia argentea（Boraginaceae 科）中的一种解毒活性化合物。这种植物在日本冲绳被当地用作治疗毒蛇 Trimeresurus flavoviridis（虎蛇）毒液中毒的解毒剂。本文提供了 RA 中和蛇毒出血作用的机制证据。通过使用几种蛇毒来检测抗出血活性。通过 SDS-PAGE 检测 RA 对 T. flavoviridis 毒液中纤维蛋白原水解和胶原蛋白水解活性的抑制作用。在存在或不存在 RA 的情况下给予毒液后，通过显微镜进行组织病理学研究。结果发现 RA 能显著中和蛇毒引起的出血、纤维蛋白原溶解、细胞毒性和 IV 型胶原活性消化。此外，RA 抑制了 T. flavoviridis 毒液在病理切片中引起的出血和中性粒细胞浸润。这些结果表明 RA 抑制了毒液的大部分出血作用。这些发现表明迷迭香酸有望在中和具有热稳定性的蛇毒方面提供治疗益处。
