■疼痛通常会导致生理和心理上的一系列异常变化,这可能导致疾病甚至死亡。药物治疗是疼痛缓解和管理的最基本和最常用的方法。有趣的是,目前,据报道,数百种中药被用于缓解疼痛,其中大多数是单体制剂,已经发展成为新的止痛药。延胡索是这些药物之一的代表,可用于缓解疼痛。
目的:本研究旨在确定延胡索衍生单体的镇痛作用和潜在靶标,并探讨任何可能的相关心脏危险因素。
方法:在本研究中,来自延胡索的四种单体(四氢巴马汀,Corydaline,普罗托品,脱氢紫藤碱)进行了体内测试,使用福尔马林诱导的疼痛模型来确定它们的镇痛特性。还使用全细胞膜片钳记录和心肌酶测定来确定它们的潜在靶标。
结果:结果表明,所有单体均表现出镇痛活性,并抑制峰值电流,促进了Nav1.7的激活和失活阶段,这表明Nav1.7可能参与了延胡索的镇痛机制。Protopine增加肌酸激酶-MB(CK-MB)的水平并抑制峰值电流,促进了Nav1.5的激活和失活阶段,表明Nav1.5可能参与了与普托品治疗相关的心脏风险。
结论:这些数据表明,延胡索乙素的镇痛效果最好,心脏风险最低。因此,电压门控钠通道(VGSCs)可能是延胡索的主要作用靶点。这项研究,因此,为未来研究和使用中药缓解疼痛提供了有价值的信息。
UNASSIGNED: Pain often causes a series of abnormal changes in physiology and psychology, which can lead to disease and even death. Drug therapy is the most basic and commonly used method for pain relief and management. Interestingly, at present, hundreds of traditional Chinese medicines have been reported to be used for pain relief, most of which are monomer preparations, which have been developed into new painkillers. Corydalis yanhusuo is a representative of one of these medicines and is available for pain relief.
OBJECTIVE: This study aims to determine the analgesic effect and the potential targets of the monomers derived from Corydalis yanhusuo, and to explore any possible associated cardiac risk factors.
METHODS: In this study, four monomers derived from Corydalis yanhusuo (tetrahydropalmatine, corydaline, protopine, dehydrocorydaline) were tested in vivo, using the formalin-induced pain model to determine their analgesic properties. Their potential targets were also determined using whole cell patch clamp recordings and myocardial enzyme assays.
RESULTS: The results showed that all monomers showed analgesic activity and inhibited the peak currents, promoted the activation and inactivation phases of Nav1.7, which indicating that Nav1.7 might be involved in the analgesic mechanism of Corydalis yanhusuo. Protopine increased the level of creatine kinase-MB (CK-MB) and inhibited the peak currents, promoted the activation and inactivation phases of Nav1.5, indicating that Nav1.5 might be involved in the cardiac risk associated with protopine treatment.
CONCLUSIONS: These data showed that tetrahydropalmatine produced the best analgesic effect and the lowest cardiac risk. Thus, voltage gated sodium channels (
VGSCs) might be the main targets associated with Corydalis yanhusuo. This study, therefore, provides valuable information for future studies and use of traditional Chines medicines for the alleviation of pain.