An Exploration On The Mechanism Of Antidepressant Of Chaigui Fang Extract

Rationales: Depression,as a mood disorder with serious harm to human health,not only adds social burden,but also depletes medical resources.At present,the main clinical interventions are chemical drugs,but there are also many problems in the treatment,such as slow onset,long medication cycle,poor efficacy,easily lead to gastrointestinal dysfunction,sexual dysfunction and other adverse reactions.In recent years,studies have found that Chinese herbal compound has obvious advantages in the treatment of depression,not only can treat the main symptoms of depression,but also can improve the symptoms,greatly improving the compliance of clinical treatment.Therefore,it is of great significance to develop a new generation of anti-depressant traditional Chinese medicines that can treat the main symptoms of depression and improve the symptoms.Chaigui Fang is a new prescription based on this group's method of systematic solvent extraction,pharmacodynamic screening,and fingerprint analysis,and after phasing out Xiaoyao San through the attribution of medicinal ingredients and the clinical observation of Yuanfang decoction.Based on this recipe,Chaigui Fang extract was prepared by a combination of ethanol extraction and water extraction and alcohol precipitation.The results of previous pharmacological experiments have found that Chaigui Fang extract not only has a clear antidepressant effect,but also has the pharmacodynamic characteristics of improving gastrointestinal function and sexual dysfunction.This study is sufficient to establish a basis for the determination of monoamine neurotransmitters,HPA axis-related hormones,gastrointestinal function-related hormones,and sexual function-related hormones in serum samples from chronic mild unpredictable stress(CUMS)depression-like rats.The anti-depression mechanism of Chaigui Fang extract and its pharmacodynamic characteristics and mechanism.Objective: 1.Based on the antidepressant effect and drug efficacy of Chaigui Fang extract,the effects of Chaigui Fang extract on monoamine neurotransmitters,HPA axis,gastrointestinal hormones and sex hormones were discussed.2.Based on the correlation analysis of monoamine neurotransmitters,HPA axis-related hormones and comprehensive behavioral indicators,the biological pathways closely related to the antidepressant efficacy of Chaigui Fang extract were sought to elucidate the antidepressant effects and pharmacological mechanisms.Content and methods: 1.Collect the serum samples of the previous CUMS efficacy test,monoamine neurotransmitters(Trp?5-HT?5-HIAA?Tyr ? DA ? NE)were determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-MS/MS)and HPA axis-related hormones(CRH?ACTH?CORT)were determined by enzyme-linked immunosorbent assay(ELISA).2.The gastrointestinal hormones(GAS,MTL)and sex hormones(T,E2)were determined by enzyme-linked immunosorbent assay(ELISA).3.The correlation analysis was made between monoamine neurotransmitters,HPA axis-related hormones,and comprehensive indicators of behavior(weight,sugar-water preference,number of crossings,and number of standings).Results: 1.Monoamine neurotransmitter determination results:(1)Compared with the blank control group,serum Trp and 5-HT levels in the serum of the model group significantly decreased,and 5-HIAA levels increased significantly(P<0.05).Compared with the model group,each administration group can increase the content of Trp and 5-HT in different degrees and reduce the content of 5-HIAA,indicating that the antidepressant mechanism of each drug has similar mechanism,that is to increase serum 5-HT metabolism the content of Trp and the decrease of 5-HIAA content to increase the 5-HT content exert an antidepressant effect.Compared with venlafaxine and Shuganjieyu,the Chaigui Fang extract reduced the amount of 5-HT to 5-HIAA,indicating that Chaigui Fang extract is more effective in inhibiting monoamine oxidase(MAO)activity;(2)Compared with the blank control group,the levels of Tyr and NE in serum of the model group were significantly decreased(P<0.05).Compared with the model group,Chaigui Fang extract high-dose group,venlafaxine group and Shuganjieyu group can increase the content of Tyr and NE in different degrees,indicating that that the antidepressant mechanism of Chaigui Fang extract is similar to that of venlafaxine and Shuganjieyu,that is to increase anti-depression effect by increasing Tyr content in serum NE metabolic pathway and increasing NE content.DA is an intermediate metabolite of Tyr and NE on the NE metabolic pathway.As a result,there was no significant difference in DA content between the experimental groups(P>0.05).One possibility is that the CUMS model is insensitive to DA;the second may be related to DA.The pathway is metabolically related(DA can also be metabolized into DOPAC and HVA within neurons).In summary,it was shown that Chaigui Fang extract may exert its antidepressant effect by regulating the abnormality of 5-HT and NE metabolic pathways,thereby increasing serum 5-HT and NE levels.2.HPA-related hormone determination results:(1)In terms of ACTH: Compared with the blank control group,ACTH levels in the model group increased significantly(P<0.01).Compared with the model group,ACTH levels were significantly decreased in all groups(P<0.05,P<0.01);(2)In terms of CORT: compared with the blank control group,the CORT content of the model group increased significantly(P <0.01).Compared with the model group,each group could significantly reduce the content of CORT(P<0.01).The effect of Chaigui Fang extract on reducing ACTH and CORT was similar to that of Shuganjieyu group,the venlafaxine group had the best effect,indicating that Chaigui Fang extract has a better effect on the hyperfunction of HPA axis in CUMS depression-like rats.3.Gastrointestinal hormones and sex hormones test results: Compared with the blank control group,the GAS,MTL,T,and E2 levels in the model group were significantly increased(P<0.01),but the contents of GAS,MTL,T,and E2 in the serum of the CUMS model group were generally significant reduce by consulting relevant literature.Therefore,the results of this study need further verification.4.The results of the comprehensive behavioral indicators show: Compared with the blank control group,the comprehensive index of behavior in the model group was significantly reduced(P<0.01).Compared with the model group,the comprehensive index of behavior in each group was significantly higher(P<0.01),indicating that it is feasible to use the comprehensive behavioral indicators to determine the depression-like symptoms and drugs to improve depression-like effects.The results of the correlation analysis between the anti-depressive biochemical indicators and the behavioral comprehensive indicators show that: HPA axis hormones(ACTH,CORT),monoamine neurotransmitters(NE,5-HIAA)and ethological indicators were highly correlated(relevance was: CORT>ACTH>NE>5-HIAA).When depressive symptoms appear,the changes of CORT,ACTH,NE,and 5-HIAA are more obvious,and they are most likely to be the markers of depression disease and the anti-depressant drug efficacy markers;besides,NE,5-HIAA,Trp and ACTH are correlated.Higher,NE,5-HIAA,Trp correlates with CORT,indicating that monoamine neurotransmitters interact with HPA axis hormones,both of which induce,aggravate,or ameliorate depression-related symptoms through neuro-endocrine pathways.Conclusion:(1)Chaigui Fang extract has an ameliorating effect on 5-HT and NE reduction caused by CUMS-induced abnormalities in 5-HT and NE metabolic pathways and HPA axis hyperactivity.Its antidepressant mechanism may be related to the regulation of 5-HT and NE metabolic pathways,HPA axis function is related to hyperactivity;(2)The mechanism of action of Chaigui Fang extract on improving gastrointestinal function and sexual dysfunction efficacy mechanism research data and literature reports have low consistency and need to be re-examined;(3)Comprehensive indicators of behavior have some reference value in distinguishing depression-like symptoms and evaluation of antidepressant efficacy.Correlative analysis of biochemical indicators can provide more convenient methods for finding depressive disease markers and antidepressant drug efficacy markers.