Laboratory for Molecular Biodiscovery, Department of Pharmaceutical & Pharmacological Sciences, KU Leuven - University of Leuven , 3000 Leuven, Belgium.
ACS Chem Neurosci. 2013 Nov 20;4(11):1479-87. doi: 10.1021/cn400140e. Epub 2013 Sep 6.
Danshen or Chinese red sage (Salvia miltiorrhiza, Bunge) is used by traditional Chinese medicine (TCM) practitioners to treat neurological, cardiovascular, and cerebrovascular disorders and is included in some TCM formulations to control epileptic seizures. In this study, acetonic crude extracts of danshen inhibited pentylenetetrazol (PTZ)-induced seizure activity in zebrafish larvae. Subsequent zebrafish bioassay-guided fractionation of the extract resulted in the isolation of four major tanshinones, which suppressed PTZ-induced activity to varying degrees. One of the active tanshinones, tanshinone IIA, also reduced c-fos expression in the brains of PTZ-exposed zebrafish larvae. In rodent seizure models, tanshinone IIA showed anticonvulsive activity in the mouse 6-Hz psychomotor seizure test in a biphasic manner and modified seizure thresholds in a complex manner for the mouse i.v. PTZ seizure assay. Interestingly, tanshinone IIA is used as a prescription drug in China to address cerebral ischemia in patients. Here, we provide the first in vivo evidence demonstrating that tanshinone IIA has anticonvulsant properties as well.
丹参或中国红参（丹参，Bunge）被传统中医（TCM）从业者用于治疗神经、心血管和脑血管疾病，并包含在一些 TCM 配方中以控制癫痫发作。在这项研究中，丹参的丙酮粗提取物抑制了斑马鱼幼虫中戊四氮（PTZ）诱导的惊厥活动。随后，对提取物进行了基于斑马鱼生物测定的分步分离，得到了四种主要的丹参酮，它们在不同程度上抑制了 PTZ 诱导的活性。其中一种活性丹参酮，丹参酮 IIA，还降低了 PTZ 暴露的斑马鱼幼虫大脑中的 c-fos 表达。在啮齿动物惊厥模型中，丹参酮 IIA 以双相方式在小鼠 6-Hz 运动性惊厥试验中表现出抗惊厥活性，并以复杂的方式改变了小鼠静脉内 PTZ 惊厥试验中的惊厥阈值。有趣的是，丹参酮 IIA 在中国被用作处方药，用于治疗患者的脑缺血。在这里，我们提供了第一个体内证据，证明丹参酮 IIA 也具有抗惊厥特性。
