Screening Of Active Ingredients And Mechanism For Sedative And Hypnotic Action Of Acanthopanax Senticosus

With the increasing pace of society,the pressure of modern people’s lives is also increasing.More and more people have symptoms of insomnia,which seriously affect people’s daily life and physical health.At present,the main drugs for insomnia are benzodiazepines,antidepressants,antipsychotics and antihistamines.However,these commonly used sedative and hypnotic drugs are often accompanied by various side effects,such as drowsiness,dizziness,fatigue,anxiety,etc.And it is easy to cause dependence and addiction of the user,and long-term use will cause serious harm to the human body.Modern research has found that many Traditional Chinese Medicines contain active ingredients for sedative and hypnosis,and these natural products have fewer adverse reactions,which have broad prospects for development and application.At present,there are more than 90 kinds of Traditional Chinese Medicines that can improve sleep.Among them,Acanthopanax Senticosus,Ziziphus jujuba,Platycladus orientalis,Acorus tatarinowii,Schisandra chinensis,Salvia miltiorrhiza,Ganoderma lucidum,Gastrodia elata,etc.are mostly used clinically.However,most of the research on these Traditional Chinese Medicines has focused on the extraction and separation of chemical components,and the mechanism of action of its active ingredients（such as gastrodin,jujuboside,schisandrin,and rhynchophylline）is still unclear.So far,there is no new medicine with the source of Traditional Chinese Medicine as the main component for the treatment of insomnia.Previous studies have demonstrated that Acanthopanax senticosus extract has the functions of protecting neurons,improving the disturbance of the human autonomic nervous system and promoting sleep.However,there are very few studies on active compounds and their mechanism of action,which seriously restricts the further research,development and utilization of Acanthopanax senticosus.Therefore,by drawing on the experience of serum medicinal chemistry of Traditional Chinese Medicine,this paper screens and verifies the molecular targets of the four metabolic components related to the central nervous system in Acanthopanax senticosus.It attempts to clarify the mechanism of Acanthopanax Senticosus for sedative and hypnosis at the molecular level.In this thesis,four plasma effective constituents of Acanthopanax senticosus（syringin,hyperoside,ciwujianoside E,1,5-dicaffeoylquinic acid）were screened using the cell models with high expression of 9 receptors(5HT_1B,5HT_2A,MT₁,MT₂,D₁,D₂,D₃,OX₁ and OX₂)related to sedative and hypnosis.Then,Cellular Thermal Shift Assay（CETSA）was used to study the binding of the compound to the target protein.The results showed that among the plasma effective constituents of Acanthopanax senticosus,ciwujianoside E activated the phosphorylation level of ERK mediated by the MT₂ overexpression cell model in a dose-dependent manner.It showed that ciwujianoside E exerted its effect through the MT₂receptor.The CETSA experiments of cells and lysates proved that ciwujianoside E combined with MT₂ receptor.It shows that melatonin MT₂ receptor is the target protein of ciwujianoside E,which provides a scientific basis for the development of sedative and hypnotic drugs with strong specificity and clear targets.