Studies On The Antidepressant Effect And Meehanisms Of Saikosaponina

Depression is a disorder of impaired emotion regulation.Sustained negative affect and a persistent reduction in positive affect are the hallmark features of a diagnosis of a major depressive episode. it has become common diseases harmful to human health, social problems and economic losses caused by depression are very serious. Consequently,the researchers have paid more attention to pathogenesy and therapy of depression, however, its mechanism is not clear so far. Indeed, studies have suggested that depression is closely related to monoamine neurotransmitters, neurotrophic factors, signal transduction and other factors. The majority of drug treatment rely to chemotherapy, antidepressant drugs commonly used at present have too much shortage, such as drug resistance, adverse effect and so on. From this perspective, we need to find out a new type of antidepressant drugs, while the vegetable drug have stable antidepressant curative effect and few adverse effect. Bupleurum is a traditional drug of frequently used in our country, we extracted the major active component of bupleurum-saikoside.Then, investigated its antidepressant effect and corresponding mechanisms based on depression animal models.1. establishment of depression rat model and observation of rats′ethology variation cured by saikoside.Two classical type included stress and raised alone were applied in our study, we raised the rats alone with each other in a single cage, this method deprived the characteristics of rat's social life. and the rats were given a series of unpredictable medium intensity stress which made them depressive state. weight gain, sacchar consumption, open field test, swim aplanetic time were used to assess the depressive extent.Then observed the index above mentioned after treatment of saikoside.According to open-field test score, we selected 60 rats whose score were proximalis, divided them into 6 groups randomly, each group have 10 rats. The 6 groups were saikoside low dose group(SsLDG 5ml/kg), saikoside middle dose group(SsMDG 10ml/kg), saikoside high dose group(SsHDG 15ml/kg), depression group(1ml liquor natrii chloridi isotonicus), fluoxetine group, normal group. The normal group were raised together, other rats were raised lonely with each other. We used 7 different stimulates on them, a stimulate were used once a day. 28days later, drug groups were given corresponding drug, different dose of saikoside and fluoxetine.In the 56days of experiment, the stress stimulate used on rats were successive. Record the weight gain once a week, sacchar consumption, open field test and swim aplanetic time fortnightly.After 4 weeks of experiment, the result suggested that the rats'body weight gain of depression model group were slow, sacchar consumption, open field test score were tapered, swim aplanetic time were increased. Compared with normal group, the differences were significant (P<0.05).The results illustrated that our depressive rat model were successful. After 56days of experiment, the differences between SsMDG, SsHDG and fluoxetine group were not significant(P>0.05), compared with depressive rat group,the differences were significant(P<0.05).The results suggested that saikoside could improve rat's appetite, curiosity and despair degree in dangerous condition. Saikoside have outstanding effect of curing depression, and the drug action of it is similar with fluoxetine.2. Influence of saikosaponina on monamine neurotransmitters and the corresponding metabolin compositions in depressed rats'brainExisting findings showed that morbidity of depressive disorder were closely correlated with monoamine neurotransmitter and its corresponding metabolin compositions, such as homovanillic acid(HVA), noradrenaline(NE), dihydroxyphenylethylamine(DA), 5-hydroxy- tryptamine(5-HT).The high performance liquid chromatography was applied to investigate the influence of the saikosaponina on monamine neurotransmitter in the depressed rats'brain. It is shown from analytical results that in the depressed rats'brain, the contents of homovanillic acid, noradrenaline, dihydroxyphenyl ethylamine and 5-HT increase in the presence of the saikosaponin A. These results can help to clarify the mechanism of saikosaponin A in curing the depression. At the end of the experiment, take out of the rats'brain on ice quickly.Then put the brain into homogenizer, add perchloric acid, homogenate on waterbath, take out of the homogenate into centrifuge tube, put them into refrigerated centrifuge, after a few time, take the clear supernatant into.condition of -70℃. The high performance liquid chromatography and fluorescence detection was applied to investigate the variation of HVA, NE, DA, 5-HT in the rats'brain.Experimental result showed that the content of HVA, NE, DA and 5-HT in depression rats'brain were degraded compared with the normal group. While the content of them in saikoside group were higher than depression group, the results were similar to fluoxetine group. So we found that our depression rats model was successful which used alonely raised and medium intensity stress, and the monoamine neurotransmitter in brain were degraded, this result confirmed the neurotransmitter hypothesis of depression. At the same time, we also found that saikoside could reversed the variation of HVA, NE, DA, 5-HT in the rats'brain.That may be the mechanism of antidepression of saikoside.3. Influence of saikosaponina on BDNF expression in depressed rats'cornu ammonis.Neurotrophy hypothesis presumes that the loss of BDNF level in patients'brain can cause depression, heightening the BDNF level used various kinds of approach can treat the depression. RT-PCR and immunohistochemical methods were applied to investigate the influence of the saikosaponina on brain-derived neurotrophic factor in rats'brain, we want to find its antidpression effect and possible mechanisms.We found that the cellula nervosa disposed indiscriminate and pultaceous, part of caryon was destroyed in depressed rats'cornu ammonis. The cell population of them was fewer than normal group, masculine BDNF cells were degraded significantly, expression was weakened, size of cells was not uniformity, collocation was anomalism. While the cellula nervosa of SsMDG and SsHDG rats'cornu ammonis were completed, collocation was regularity, drum dyeing was dark, content of BDNF was high. Compared with fluoxetine group, the difference is not significant. It showed that some cellula nervosa was died and destroyed in depressed rats'brain, and content of BDNF was degraded. Saikoside could protect cellula nervosa in cornu ammonis,set up the content of BDNF. That may be the mechanism of antidepression of saikoside.Above all, we used stress and raising alone in our study,extended experiment time, depressed rats model were establishened successfully. The depressed rats'body weight gain, sacchar-consumption and open-field test score degraded,swimming immobility time increased. This type of depression model is stable. It is valuable on the study of depression nosogenesis and thymoleptics. Saikoside can improve depressed appearance, especially when used middle and high dose, the effect is optimization. The nosogenesis of depressive disorder is related with the content of HVA, NE, DA, 5-HT and BDNF in rats'brain. Saikoside can regulate them. That may be the mechanism of antidepression of saikoside.