Screening Of Active Constituents Of Traditional Chinese Medicine With Dopamine Receptor As Target

While modern life brings efficiency and convenience to people,it also brings many health problems.Insomnia is one of the most common problems.Insomnia is a comprehensive neurological disorder disease characterized by difficulty falling asleep,decreased sleep quality and reduced sleep time.Long-term insomnia can lead to memory,attention,immunity decline,and induce anxiety,depression et al.even more,insomnia can be an important trigger for neurodegenerative diseases such as Alzheimer's and Parkinson's syndrome.Human sleep is regulated by multiple receptors in the central nervous system.Dopamine receptors are a very important class.Among the dopamine receptor subtypes,the D₂ subtype plays an important role in regulating sleep,mood,nerve excitation and inhibition.Small molecule drugs targeting D₂ may have functions that regulate nerve excitability,regulate mood,and sleep.Since ancient times,China has had a valuable traditional Chinese medicine tradition and has rich herbal medicine resources.The target discovery and mechanism research of traditional Chinese medicine extracts and compounds derived from traditional Chinese medicines are effective ways to promote the development of new drugs.Based on the laboratory-constructed dopamine receptor D2,D3,orexin receptor OX2,melatonin receptor MT2 stable cell line,57 compounds were screened,and 13targets were clearly available.A lead compound for the development of new drugs.In addition,this study also explored the mechanism of sedative and tranquillizing effect of Gastrodia elata.It was found that Gastrodia might regulate sleep by up-regulating the activity of central DA system.Gastrodin,the active constituent of gastrodia,could play a regulating role through D₂-mediated signaling pathway.There are two alternative splicing bodies in D₂:D_2L and D_2S,and they can mediate different physiological and pharmacological reactions.Another part of this study is to successfully construct two fluorescent molecular probes,D_2L and D_2S,which lay the foundation for more refined drug screening of dopamine receptor D₂.The preliminary experimental results of this study are as follows:1)Western blotting was used to identify 13 active Chinese medicine active ingredients with clear target and considerable effect.2)It was found that Gastrodia might regulate sleep by up-regulating the activity of central DA system.Gastrodin,the active constituent of gastrodia,could play a regulating role through D2-mediated signaling pathway.3)Two vector plasmids,D2L-cfp-flash and D2S-cfp-flash,were successfully constructed,and stable induced expression cell lines were screened.