| Objective:To explore pharmacological mechanism of night prescription of my tutor in treating anxiety and insomnia—Ning Xin An Shen decoction(NXAS)from different extraction methods to guide clinical drug and new drug development and theoretical support.Method:The first part adopt the research method of literature analysis,combine traditional Chinese medicine theory,reference relevant schools and different views of various doctors,sums up the typical cases and inspiration,learns the lecture materials of the instructors,the content of speech and conference,the scientific research project and articles published publicly,search the papers published by my tutor’s other students about the clinical experiences,systematically conclude summarize my tutor’s clinical experiences in emotional disease and insomnia and clinical characteristic about day-and-night prescription.The second part adopt the method of review to summarize,analyze and compare the research situations on the pathogenesis of anxiety disorders and the anti-anxiety medicine between western and Traditional Chinese Medicine to explore advantages and directions of drug research using Traditional Chinese Medicine to treat anxiety disorders in the future.The third part adopt the animal experiment to study the pharmacodynamics,pharmacology and active ingredients of NXAS,an experience of my tutor to treat anxiety and insomnia,establish the anxiety rat model by using the method of uncertain empty bottle in drinking water,set up the blank group and model group,NXAS extracted by alcohol group,NXAS extracted by water group,and lorazepam group,evaluate their anxiolytic and sedative-hypnotic effects by behavioral tests and pentobarbital sleep synergy respectively,and measure anti-anxiety drugs target with serum and brain of rats to systematically explore the pharmacological mechanism of NXAS in the treatment of anxiety disorders from the overall,tissue,and molecular levels using alcohol and water extraction.Result:The anxiety rat model is successfully reproduced using the method of uncertain empty bottle stimulation.The time,distance,and frequency in the open arm of elevated plus maze are significantly reduced.The time,distance,and frequency in the center area of the open field is obviously decreased.The time,distance,and frequency in the bright box are significantly declined,but sleep could not be effected.Further research to pharmacodynamics of NXAS found that:In the behavior,Two kind of NXAS extractions can significantly improve anxietylike behavior in rats,and the onset time is slower than western medicine.It achieved stable efficacy in weeks later,and the water extraction has better anti-anxiety effect than alcohol extraction and equal to western medicine.At the same time,NXAS alcohol extraction can significantly prolong sleep duration.Pharmacology research of NXAS found that:Pathological HE staining results show that there are different degree of tissue destruction in hippocampus,amygdala and hypothalamus in anxious rats,and NXAS extractions can protect neurons and maintain their normal morphology.In the molecular level,all three can correct the disorder of neuro-endocrine-immune system from serum and brain.In the serum of anxious rats levels of CORT and pro-inflammatory factors such as TNF-α,IL-1β,IL-6 increase significantly while NE,5-HT,GABA,Glu and anti-inflammatory cytokines IL-10 decrease significantly.In the hippocampus,amygdala,hypothalamic levels of NE,5-HT,GABA decline significantly while Glu increase significantly,and levels of GABAA receptor subunits(including α1,α2,α3,α5,γ2),5-HT1A receptors,and NMDA receptor decrease;levels of CCK in the hippocampus,amygdala,and hypothalamus decrease.NXAS alcohol extraction mainly play a role in sedation and sleep and its targets are GABAA receptor α1,γ2 subunit,5-HT1A receptor,and CCK in hippocampus and hypothalamus.NXAS water extraction mainly exerts anxiolytic effect and its target are GABAA receptor α2,α3 subunit,5-HT1A receptor and CCK in hippocampus and hypothalamus.The target of the positive control drug lorazepam are GABAA receptor α2,α3,γ2 subunits and 5HT1A receptors.Pharmaceutical research of NXAS found that:The content of jujube saponin A in NXAS of alcohol extraction is more than that of water extraction,and the content of syringin of water extraction is more than that of alcohol extraction.The content of spinosyn and rosmarinic acid was similar to that of alcohol extraction and water extraction.Conclusion:NXAS has many effects in anti-anxiety,sedative,neuroprotective and anti-inflammatory.The main effects of alcohol extraction and water extraction are different.The water extraction have strong anxiolytic effect,similar to the pharmacological mechanism and comparable efficacy of BDZ and more targets.While effect of sedative and hypnotic in alcohol extraction is strong,and no muscle relaxation,that may be different from the content of Suanzaoren saponin A and there may be dose-effect relationship,That is,low doses can make an effect of anti-anxiety,high doses can make an effect of sedation and hypnosis. |
PDF Full Text Request