| Objective:To compare the antidepressant effect and mechanism among the decoction of Xiaoyaosan (XYS) and its efficacy compositions involving SGY, YXY, JPY as well as two matched combinations XYS without YXY (XYSQYXY) and XYS without SGY (XYSQSGY), so as to interpret the relationship between efficacy compatibility and antidepressant effect. It provides experimental foundation for explaining scientific intension of XYS efficacy with soothing liver-qi stagnation (Shu Gan Jie Yu in Chinese).Methods:In this research, antidepressant effect and mechanism of XYS and its efficacy compositions were discussed and compared in terms of behavioral performance, molecular markers and systematic data analysis.①The effect of XYS and its efficacy compositions on total immobile duration (TIMD) in tail suspension test (TST) and forced swimming test (FST) and locomotor activity was observed on the basis of incentive disengagement model in mice.②The effect of XYS and its efficacy compositions on locomotor activity (including crawling distance and standing frequency), weight growth (WG), preference for1%sucrose solution (PSS), foraging latency in T-shaped maze test (FL) was observed on the basis of CUMS model in rats.③The effect of XYS and its curative efficacy compositions on locomotor activity (including crawling distance and standing frequency), weight growth (WG), preference for1%sucrose solution (PSS) and some indicators in Morris water maze test, such as escape latency (EL), retention period percentage at target quadrant (RPP), moving distance percentage at target quadrant (MDP), entering frequency percentage at target quadrant (EFP), entering frequency into escape platform (EFE) and entering frequency into valid area (EFV) was observed on the basis of CUMS model in rats.④The effect of XYS and its curative efficacy compositions on serum IL-1β (sIL-1β), IL-6(sIL-6), TNF-α(sTNF-α), IFN-γ (sIFN-γ), CRH (sCRH), Cort (sCort),5-HT (s5-HT) and BDNF (sBDNF), corticocerebral5-HT (c5-HT) and BDNF (cBDNF), hippocampal5-HT (h5-HT) and BDNF (hBDNF) in CUMS-exposed rats was determined by ELISA.⑤The effect of XYS and its curative efficacy compositions on corticocerebral IDOase (cIDOase) and Cort (cCort), hippocampal IDOase (hIDOase) and Cort (hCort) in CUMS-exposed rats was determined by ELISA. The effect of the decoction above on corticocerebral GCR-mRNA (cGCR-mRNA) and TrkB-mRNA (cTrkB-mRNA), hippocampal GCR-mRNA (hGCR-mRNA) and TrkB-mRNA (hTrkB-mRNA) in CUMS-exposed rats was measured by Real-time quantitative PCR (rt-qPCR). The effect of the decoction above on corticocerebral IL-1β (cIL-1β) and hippocampal IL-1β (hIL-1β) in model rats was detected by Western Blot (WB).⑥Correlation, cluster and effect intensity analysis of the data above were performed via SPSS17.0software.Results:(1)The effect of XYS and its efficacy compositions SGY, YXY, JPY, XYSQYXY, XYSQSGY on behaviors in model mice of incentive disengagement:Compared with control group, all of the five combinations XYS, SGY, YXY, XYSQYXY, XYSQSGY showed the ability to obviously shorten TIMD in TST-and FST-exposed mice (P<0.01), but showed no influence on locomotor activity under the same dose (P>0.05). Significant difference was not manifested among those five combinations (P>0.05). JPY had no effect on those behavioral indicators (P>0.05).(2)The effect of XYS and its efficacy compositions SGY, YXY, JPY on behaviors in model rats of CUMS:Compared with model group, increase of crawling distance, standing frequency, WG, PSS and decrease of FL were significantly manifested in groups of XYS, SGY, YXY and amitriptyline after treatment for4weeks (P<0.05or P<0.01). But JPY didn’t have the same effect on those behavioral indicators (P>0.05). The ameliorative effect of XYS and SGY on those behavioral indicators was significantly higher than that of YXY (P<0.05or P<0.01) and significant difference was not manifested between XYS and SGY (P>0.05).(3)The effect of XYS and its curative efficacy compositions SGY, YXY, XYSQYXY, XYSQSGY on behaviors in model rats of CUMS:Compared with model group, increase of crawling distance, standing frequency, WG, PSS, RPP, MDP, EFP, EFE and EFV and decrease of EL were significantly manifested in groups of XYS, SGY, YXY, XYSQYXY and XYSQSGY after treatment for4weeks (P<0.01). XYS, SGY and XYSQYXY could significantly increase WG (P<0.01) in CUMS-exposed rats. The ameliorative effect of XYS, SGY and XYSQYXY on those behavioral indicators was significantly higher than that of YXY and XYSQSGY (P<0.01). Significant difference was not manifested among XYS, SGY and XYSQYXY, the same as between YXY and XYSQSGY (P>0.05).(4)The effect of XYS and its curative efficacy compositions SGY, YXY, XYSQYXY, XYSQSGY on biochemical indexes in model rats of CUMS:①Compared with model group, decrease of serum cytokines was significantly manifested in groups of XYS, SGY, YXY, XYSQYXY and XYSQSGY after treatment for4weeks (P<0.01). XYS and SGY could significantly decrease cIL-1β and hIL-1β (P<0.05) in CUMS-exposed rats. The regulatory effect of XYS, SGY, XYSQYXY on serum cytokines was significantly higher than that of YXY and XYSQSGY (P<0.05or P<0.01). Meanwhile, significant difference was not manifested among SGY, XYS and XYSQYXY (P>0.05), the same as between YXY and XYSQSGY (P>0.05).②Compared with model group, decrease of sCRH and sCort was significantly manifested in groups of XYS, YXY and XYSQSGY after treatment for4weeks (P <0.01or P<0.05). XYS and YXY could significantly decrease cCort and hCort (P <0.05) and could remarkably increase the expression of cGCR-mRNA and hGCR-mRNA (F<0.05) in CUMS-exposed rats. Meanwhile, significant difference was not manifested among XYS, YXY and XYSQSGY (P>0.05). SGY and XYSQYXY had no impact on those indexes (P>0.05).③Compared with model group, reduction of c5-HT and h5-HT (P<0.01or P <0.05) was inhibited significantly in groups of XYS, SGY, YXY, XYSQYXY and XYSQSGY after treatment for4weeks (P<0.01or P<0.05). The improvement effect of XYS on h5-HT is highest among that of groups with decoction (P<0.01or P<0.05). The regulatory effect of XYS, SGY, XYSQYXY on those indexes was significantly higher than that of YXY and XYSQSGY (P<0.05or P<0.01). Meanwhile, significant difference was not manifested between SGY and XYSQYXY (P>0.05), the same as between YXY and XYSQSGY (P>0.05). XYS and SGY could significantly decrease the expression of cIDOase and hIDOase (P<0.05).④Compared with model group, reduction of sBDNF, cBDNF and hBDNF was inhibited significantly in groups of XYS, SGY and XYSQYXY after treatment for4weeks (P<0.01or P<0.05). Significant difference in the respective effect on sBDNF, cBDNF and hBDNF was not manifested among XYS, SGY and XYSQYXY (P>0.05). YXY and XYSQSGY had no impact on those indexes (P>0.05). XYS and SGY could significantly increase the expression of cTrkB-mRNA and hTrkB-mRNA(P<0.01or P<0.05).(5)Cluster and effect intensity analysis of behavioral and molecular indexes:①On the basis of behavioral indexes as variables, XYS, SGY and XYSQYXY were placed in the same category; YXY and XYSQSGY were placed in the same category. On the basis of biochemical indexes as variables, XYS, SGY and XYSQYXY were placed in the same category; YXY and XYSQSGY were placed in the same category. Among XYS, SGY and XYSQYXY, what’s more, SGY and XYSQYXY were placed in the same category; XYS belonged in a different classification.②The effect intensity of XYS, SGY and XYSQYXY on behavioral and molecular indexes was higher than that of YXY and XYSQSGY. XYS, SGY and XYSQYXY showed same strength on behavioral indexes, cytokines and c5-HT, but the effect intensity of XYS on h5-HT was higher than that of SGY and XYSQYXY. YXY and XYSQSGY showed same strength on those indexes. Based on behavioral research, the combination of Radix Bupleuri and Mentha haplocalyx (RB-MH) performed better function in improving locomotor activity than in improving memory and cognition, much better than in improving emotion. The combination of Radix Paeoniae Alba and Angelica sinensis (PA-AS) performed better function in improving memory and locomotor activity than in improving emotion, much better than in improving cognition. Based on mechanism research, the combination of RB-MH performed better function in modulating central5-HT targets than in modulating cytokines. The combination of PA-AS performed better function in modulating cytokines than in modulating central5-HT targets.③According to the summary of behavioral and molecular improvement, RB-MH combination was focused on the regulation of cytokines and central5-HT/BDNF/TrkB pathway. PA-AS combination was focused on the regulation of HPA axis and central Cort/GCR pathway.Conclusion:The therapy of soothing the liver represented by RB-MH combination is dominating in antidepressant effect of XYS, which to a certain extent tends to improve locomotor activity and WG, with possible mechanism of modulating central nervous function and cytokines. The therapy of nourishing the blood represented by PA-AS combination is auxiliary in antidepressant effect of XYS, which to a certain extent tends to memory and locomotor activity, with possible mechanism of modulating endocrine function and cytokines. Interaction of the two therapies carries out integrated antidepressant effect. |
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