School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Molecules. 2018 Oct 10;23(10):2585. doi: 10.3390/molecules23102585.
W. T. Wang () has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on , the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from to inhibit dopamine-induced dopamine D₁ receptor activity. By using our established cyclic adenosine monophosphate (cAMP)-response element (CRE)-luciferase reporter gene assay system, we identified eight alkaloids from with D₁ receptor antagonistic activities. We next validated the activities of these compounds using fluorometric imaging plate reader (FLIPR) assay by measuring the intracellular Ca change. Six out of eight compounds, including tetrahydropalmatine, corydaline, 13-methyldehydrocorydalmine, dehydrocorybubine, dehydrocorydaline, and columbamine, can be confirmed for their inhibitory activities. The dopamine-receptor-antagonistic effects of four compounds, including 13-methyldehydrocorydalmine, dehydrocorydaline, columbamine, and corydaline, are reported for the first time. The present study provides an important pharmacological basis to support the traditional use of in China.
王不留行（W. T. Wang）在中国传统上被用于治疗药物成瘾和缓解疼痛。在我们之前的研究中，我们表明该提取物可阻断多巴胺受体，表明其药理活性主要归因于其某些成分对多巴胺受体的拮抗作用。作为我们正在进行的关于黄连的研究的一部分，本研究的目的是建立一种高通量且低成本的筛选检测系统，并测试从黄连中分离出的生物碱抑制多巴胺诱导的多巴胺 D₁受体活性的能力。通过使用我们建立的环磷酸腺苷（cAMP）反应元件（CRE）-荧光素酶报告基因检测系统，我们从黄连中鉴定出 8 种具有 D₁受体拮抗活性的生物碱。接下来，我们通过测量细胞内 Ca²⁺变化，使用荧光成像板读数器（FLIPR）检测系统验证了这些化合物的活性。在 8 种化合物中，有 6 种，包括延胡索乙素、黄连碱、13-甲基脱氢黄连碱、脱氢卡维丁、脱氢黄连碱和小檗碱，可证实其具有抑制作用。首次报道了 4 种化合物，包括 13-甲基脱氢黄连碱、脱氢黄连碱、小檗碱和黄连碱，具有多巴胺受体拮抗作用。本研究为支持中国传统上使用黄连提供了重要的药理学依据。
