Hydroxycinnamic acid amides from Scopolia tangutica inhibit the activity of M1 muscarinic acetylcholine receptor in vitro.
Hydroxycinnamic acid amides from Scopolia tangutica inhibit the activity of M1 muscarinic acetylcholine receptor in vitro.
复制标题
唐古特萼羟基肉桂酰胺体外抑制 M1 毒蕈碱乙酰胆碱受体活性
DOI：
10.1016/j.fitote.2015.11.007
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发表时间：
2016-01
期刊：
影响因子：
3.4
通讯作者：
Civelli O
中科院分区：
文献类型：
--
作者：
Zhang Y;Long Z;Guo Z;Wang Z;Zhang X;Ye RD;Liang X;Civelli O
唐古特东芝提取物在西藏和青海中国地区传统上被用作解痉剂、镇静剂和止痛剂。然而，人们对它们的活性成分知之甚少。我们最近从这些提取物中分离出了五个新的羟基肉桂酸(HCA)酰胺和两个已知的HCA酰胺，其中一个是肉桂酸酰胺。在这项研究中，我们评估了它们与粗提物一起抑制卡巴胆碱诱导的M1乙酰胆碱受体活性的能力。用稳定表达重组人M1受体的中国仓鼠卵巢细胞(CHO-M1细胞)评价其抗胆碱能作用。用FLIPR系统监测细胞内钙离子的变化。5种HCA酰胺类化合物和唐古特沙门氏菌粗提物对M1受体的抑制作用呈剂量依赖性。这些发现表明，HCA酰胺是唐古特沙门氏菌M1受体抑制原理的一部分。由于通过抑制M1受体阻断副交感神经冲动传递可减轻平滑肌痉挛，我们的发现为唐古特链霉菌治疗痉挛的传统用法提供了分子解释。
Scopolia tangutica Maxim (S. Tangutica) extracts have been traditionally used as antispasmodic, sedative, and analgesic agents in Tibet and in the Qinghai province of China. Their active compositions are however poorly understood. We have recently isolated five new hydroxycinnamic acid (HCA) amides along with two known HCA amides, one cinnamic acid amide from these extracts. In this study, we evaluate their abilities to inhibit carbacol-induced activity of M1 muscarinic acetylcholine receptor along with the crude extracts. Chinese hamster ovary cells stably expressing the recombinant human M1 receptor (CHO-M1 cells) were employed to evaluate the anticholinergic potentials. Intracellular Ca2+ changes were monitored using the FLIPR system. Five HCA amides as well as the crude S. Tangutica extract displayed dose-dependent inhibitory effects against M1 receptor. These findings demonstrate that HCA amides are part of the M1 receptor-inhibiting principles of S. tangutica. Since blockade of parasympathetic nerve impulse transmission through the inhibition of the M1 receptor lessens smooth muscle spasms, our findings provided a molecular explanation for the traditional use of S. Tangutica against spasm.