Key Laboratory of TCM-Information Engineer of State Administration of TCM, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China.
Int J Mol Sci. 2018 Jan 10;19(1):163. doi: 10.3390/ijms19010163.
The metabotropic glutamate receptors (mGluRs) are known as both synaptic receptors and taste receptors. This feature is highly similar to the Property and Flavor theory of Traditional Chinese medicine (TCM), which has the pharmacological effect and flavor. In this study, six ligand based pharmacophore (LBP) models, seven homology modeling models, and fourteen molecular docking models of mGluRs were built based on orthosteric and allosteric sites to screening potential compounds from Traditional Chinese Medicine Database (TCMD). Based on the Pharmacopoeia of the People's Republic of China, TCMs of compounds and their flavors were traced and listed. According to the tracing result, we found that the TCMs of the compounds which bound to orthosteric sites of mGluRs are highly correlated to a sweet flavor, while the allosteric site corresponds to a bitter flavor. Meanwhile, the pharmacological effects of TCMs with highly frequent flavors were further analyzed. We found that those TCMs play a neuroprotective role through the efficiencies of detumescence, promoting blood circulation, analgesic effect, and so on. This study provides a guide for developing new neuroprotective drugs from TCMs which target mGluRs. Moreover, it is the first study to present a novel approach to discuss the association relationship between flavor and the neuroprotective mechanism of TCM based on mGluRs.
代谢型谷氨酸受体（mGluRs）既是突触受体，也是味觉受体。这一特性与中药（TCM）的药性和味道理论高度相似，具有药理作用和味道。在这项研究中，基于 mGluRs 的正构和变构位点，构建了六个配体基药效团（LBP）模型、七个同源建模模型和十四个分子对接模型，以从中药数据库（TCMD）中筛选潜在化合物。根据《中华人民共和国药典》，追踪并列出了化合物及其味道的中药。根据追踪结果，我们发现与 mGluRs 的正构位点结合的化合物的中药与甜味高度相关，而变构位点则与苦味相对应。同时，还进一步分析了具有高频味道的中药的药理作用。我们发现，这些中药通过消肿、促进血液循环、镇痛等作用发挥神经保护作用。本研究为开发以 mGluRs 为靶点的新型神经保护药物提供了指导。此外，这是首次基于 mGluRs 提出一种新方法来探讨味道与中药神经保护机制之间的关联关系。
