Investigations On The Antidepressant Active Constituents And Mechanism Of Kaixinsan

Text: Kaixinsan(KXS) is a fundamental prescription to treat sentimental diseases in traditional Chinese medicine, which is composed of Radix Ginseng, Poria, Radix polygala and Rhizoma acoru tatarinowii. It was recorded in many ancient traditional Chinese medicine books and was used to treat sentimental diseases, which was similar to depression in the West medicine. It has been proved to be effective in clinical to treat depression or anxiety for a long time. In order to find the best compatibility and active components of KXS for treating depression, elucidate its mechanism on anti-depression, methods of chemistry and pharmacology were combined to systematically study KXS.Prepared forced swimming mice model and suspend tail mice model, through two technologies: ingredients combination after each active principle extracted respectively and all crude drugs decocted together, anti-depression effect of three formulas of KXS from 《Qian Jin Yao Fang》 , 《Gu Jin Lu Yan》 and 《Tai Ping Hui Min He Ji Ju Fang》 was investigated. Results indicated that KXS of 《Tai Ping Hui Min He Ji Ju Fang》 composed of 3 liang Ginseng and 3 liang Tuckahoe and 2 liang polygala and 2 liang Acoru tatarinowii had the best antidepressant effect compared to KXS of 《Qian Jin Yao Fang》 and 《Gu Jin Lu Yan》 . Furthermore, KXS by co-decoct had the better curative effect than ingredients combination after each active principle extracted respectively.On the basis of screening, rat forced swimming model and 5-HTP induced head-twitches model were used to assess the antidepressant effect of KXS of 《Tai Ping Hui Min He Ji Ju Fang》 . Results showed that KXS of 《Tai Ping Hui Min He Ji Ju Fang》 significantly decreased the accumulative immobility time in rat forced swimming test, increased the times of 5-HTP induced head-twitches in mice.Taking forced swimming mice as model, central neurotransmitter in brain and glucocorticoid (GC) content in plasma at different time after taking KXS of ?Tai Ping Hui Min He Ji Ju Fang)) were determined. Results manifested that KXS can decrease GC content in plasma, increase serotonin(5-HT) and norepinephrine(NE) content in brain, degrade specific value 5-HT/5-HIAA significantly. However, KXS has no notable influence on dopamine (DA) content in "force swimming" mice brain.Through solvent extraction and macroporous adsorptive resins adsorption, water and gradient ethanol elute, "force swimming" and "suspend tail" experiments was combined to screen active components of KXS on anti-depression. Components extracted from KXS by 50% ethanol and eluted by 30%~60% ethanol were testified active components. TLC and HPLC analysis indicated that these components included some ingredients of ginseng and polygala. Using rat everted gut sac model, the ingredients that can be absorbed by intestine were proved to be panaxsaponin Rb1, Rb2, Rg1, Rg2, Rc, Rf, Ro, N-R2 and feruloylsucrose, Sinapoylsucrose, 3,4,5-trimethoxycinnamoylsucrose, disinapoylsucrose, tenuifoliside A, tenuifoliside C in polygala.Using rat model that was prepared by CUMS and raising alone, effect of active components of KXS on ethology, ultramicrostructure and expression of P-CREB, BDNF of hippocampus of depressive model rats was observed. Results showed that active components of KXS can promote a gain in weight and sacchar-intake, increase scores of crossing and rearing, improve depressive symptom of CUMS model rats notablely. KXS can lighten neuron injury caused by stresss in CA3 area of hippocampus, increase the expression of P-CREB and BDNF of model rats' hippocampus.Morris Water Maze method was used to evaluate protective effect of KXS on the chronic stress induced impairment of learning and memory in mice. Results showed that KXS could improve ability of learning and memory in chronic stress mice.