Division of Pharmacy, School of Life and Health Sciences, Aston University, Birmingham, UK.
J Pharm Pharmacol. 2010 Feb;62(2):257-62. doi: 10.1211/jpp.62.02.0014.
Curcuma zedoaroides A. Chaveerach & T. Tanee, locally known as Wan-Paya-Ngoo-Tua-Mia, is commonly used in the North-Eastern part of Thailand as a 'snakebite antidote'. The aim of this study was to isolate the active compound from the rhizome of C. zedoaroides, to determine its structure and to assess its antagonistic activity in vitro and in vivo against King cobra venom.
The active compound was obtained from C. zedoaroides by extraction with acetone followed by purification using column chromatography; its X-ray structure was determined. Its inhibition of venom lethality was studied in vitro in rat phrenic nerve-hemidiaphragms and in vivo in mice.
The acetone extract of the Curcuma rhizomes contained a C20 dialdehyde, [2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde, as the major component. The isolated curcuma dialdehyde was found active in vitro and in vivo for antivenin activity against the King cobra venom. Using isolated rat phrenic nerve-hemidiaphragm preparations, a significant antagonistic effect on the inhibition of neuromuscular transmission was observed in vitro. Inhibition on muscle contraction, produced by the 4 microg/ml venom, was reversed by 2-16 microg/ml of Curcuma dialdehyde in organ bath preparations over a period of 2 h. Mice intraperitoneally injected with 0.75 mg/kg venom and dialdehyde at 100 mg/kg had a significantly increased survival time. Injection of Curcuma dialdehyde (100 mg/kg) 30 min before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group.
The in vitro and in vivo evaluation confirmed the medicinal use of traditional snake plants against snakebites. The bioactivity is linked to an isolated molecule and not a result of synergistic effects of a mixture. The active compound was isolated and the structure fully elucidated, including its stereochemistry. This dialdehyde is a versatile chemical building block and can be easily obtained from this plant source.
姜黄属植物 C. zedoaroides，在泰国东北部地区俗称 Wan-Paya-Ngoo-Tua-Mia，常被用作“蛇伤解毒剂”。本研究旨在从该植物的根茎中分离出活性化合物，确定其结构，并评估其在体外和体内对眼镜王蛇毒液的拮抗活性。
用丙酮从 C. zedoaroides 中提取活性化合物，然后用柱层析法进行纯化；其 X 射线结构已确定。在大鼠膈神经-半膈肌体外和小鼠体内研究其对毒液致死性的抑制作用。
姜黄根茎的丙酮提取物含有一种 C20 二醛，[2-（5,5,8a-三甲基-2-亚甲基-十氢萘-1-基）-亚乙基]-琥珀二醛，作为主要成分。分离出的姜黄二醛在体外和体内均对眼镜王蛇毒液具有抗蛇毒活性。使用分离的大鼠膈神经-半膈肌制剂，在体外观察到对神经肌肉传递抑制的显著拮抗作用。在器官浴制剂中，2-16 µg/ml 的姜黄二醛可逆转 4 µg/ml 毒液引起的肌肉收缩抑制，作用持续 2 小时。腹腔注射 0.75 mg/kg 毒液和 100 mg/kg 姜黄二醛的小鼠，存活时间显著延长。在皮下注射毒液前 30 分钟注射姜黄二醛（100 mg/kg），与对照组的 0%相比，2 小时后存活率达到 100%。
体外和体内评价证实了传统蛇类植物在蛇咬伤中的药用价值。生物活性与分离的分子有关，而不是混合物的协同作用。该活性化合物已被分离，其结构已被充分阐明，包括其立体化学。这种二醛是一种多功能的化学结构单元，可从该植物来源中轻易获得。
