ABSTRACT
This paper aimed at comparing the differences of antidepressant effects of Yueju Pill between the Balb/c mice and C57 BL/6 J mice and analyzing the effects on synaptic transmission in mice prefrontal cortex. Healthy adult Balb/c mice and C57 BL/6 J mice were randomly divided into control group and Yueju Pill group. Control group was treated with saline, Yueju Pill group was treated with single dose of Yueju Pill (13.5 g·kg-1) . The forced swimming test (FST) was measured 30 min after administration. The field excitatory postsynaptic potential (fEPSP) and long-term potentiation (LTP) of mice prefrontal cortex were detected by the electrophysiological experiment. In FST, the immobility time of Balb/c mice in Yueju Pill group was significantly lower than that in control group (P ＜ 0.01), and the immobility time of C57 BL/6 J mice showed no remarkable difference between Yueju Pill group and control group (P＞ 0.05) . In electrophysiological experiment, the percentage of slope of fEPSP in Balb/c mice in Yueju Pill group was significantly higher than that in control group (P ＜ 0.01), while there was no significantly difference in C57 BL/6 J mice between Yueju Pill group and control group (P＞ 0.05) . The LTP of Balb/c mice in Yueju Pill group was significantly increased than that in control group (P ＜ 0.01), while there was no significantly difference in LTP of C57 BL/6 J mice between Yueju Pill group and control group (P＞ 0.05) . Yueju Pill may display rapid antidepressant effect via increasing fEPSP and LTP in prefrontal cortex of Balb/c mice and then enhancing the synaptic transmission.
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Objective: To explore the effects of Yueju pill on Nitricoxide-cyclic guanosine monophosphate (NO-cGMP) signaling in mouse hippocampus. Methods: Single dose of Yueju pill was administered, and mouse hippocampi were got out after administration for 12 min, 24 min, 30 min, 3 h and 24 h. The concentrations of NO and cGMP were detected by ELISA. Other mice were randomly divided into the following groups: control group (con), L-arg group (L-arg), Yueju pill group (YJ) and L-arg+ Yueju pill group (L-arg+YJ) . Control group was treated with saline, YJ group was treated with Yueju pill (13.5 g·kg-1), and L-arg group was treated with L-arg (750 mg·kg-1) . Tail suspension test (TST) was measured30 min after administration.Results:12 min after YJ administration, the concentration of NO was significantly lower than that in control group (P ＜ 0.05) and the concentration of c GMP was also significantly lower than that in control group (P ＜ 0.05) . In the TST test, the immobility time in YJ group was significantly shorter than that in control group (P ＜ 0.01), and the immobility time in L-arg+YJ group was significantly longer than that in YJ group (P ＜ 0.01) . In open field test (OFT), the spontaneous activity of mice were not affected by administering L-arg or YJ. Conclusion: Yueju pill may rapidly alleviate depression-like behaviors of mice through regulating NO concentration, then influencing downstream cGMP and activating the NO-cGMP signaling in cells.
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This study aimed at exploring the mechanism of the rapid antidepressant effects of Yueju pill on depression of Parkinson's disease (DPD).The fast antidepressant effects of Yueju pill in this study was evaluated by behavior tests,such as open field test (OFT),tail suspension test (TST),forced swimming test (FST) and sucrose preference test (SPT) according to the modeling method of subacute DPD in the literature.In vitro experiment was implemented using PC12 cells.Moreover,the protective effects of Yueju pill on 1-methyl-4-phenylpyridinium (MPP+) induced neural injury with the engagement of cAMP response element binding protein (CREB) were expounded.As a result,it was found that the immobility time of the mice in the model group was significantly longer than that in the normal group in TST and FST tests (P ＜ 0.01),and the SPT ratio of mice in the model group remarkably decreased (P ＜ 0.01).In addition,the immobility time of DPD mice was shortened in the FST test after administering Yueju pill (P ＜ 0.05),while the SPT ratio was increased (P ＜ 0.01).Yueju pill took the effects on the third day after a single administration.The phosphorylation of CREB (p-CREB) in MPP+ induced PC12 cells was decreased in comparison with the model group,while the expression of p-CREB was up-regulated with the administration of Yueju pill (P ＜ 0.01).In conclusion,DPD was quickly mitigated after the treatment of Yueju pill,the activation of CREB signaling pathway and its neuroprotective effects may be the mechanism behind it.
ABSTRACT
Major depression is a public health problem that seriously harms individuals and the society.But one of the major shortcomings of mainstream antidepressant is the delayed onset.Recent series of studies demonstrated that,from a variety of animal models and clinical studies,classic stagnation-removing formula Yue-Ju (Y J) pill has the advantage in rapid antidepressant efficacy,which is similar to the prototype drug ketamine.It has the mechanism of rapid and sustained enhancement of neural plasticity and individual difference in response to YJ pill.The evidence of Gardenia jasminoides (Zhi-Zi) as the monarch component of YJ pill's rapid antidepressant action has also been revealed.The further in-depth research on rapid antidepressant traditional Chinese medicine (TCM) is important for providing the scientific and reliable TCM strategies to treat depression.
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Aim To observe the rapid antidepressant effect of Yuejuganmaidazao Decoction on postpatum de-pression offspring , and analyze its influence on the Akt and mTOR expression .Methods After postpartum de-pression model was established , the offsprings were randomly divided into the following groups: control group(CTL-F1,n =8), vehicle group (Veh,n =8) and YG group ( YG, n =8 ) .Veh group was treated with vehicle , YG group was treated with Yueju gan-maidazao Decoction(8.3 g· kg -1 ).Forced swimming test(FST) was measured 24 hours after single adminis-tration.The phosphorylation and total level of Akt and m-TOR in the hippocampus was detected by Western blot.Results The immobility time in YG group was significantly shorter than that in Veh group ( P <0.01 ) , and the expression of p-Akt and p-mTOR in the hippocampus was significantly increased ( P <0.05 ) .Conclusion Yuejuganmaidazao Decoction may rapidly alleviate depression-like behaviors of PPD offsprings through upregulation of Akt and mTOR ex-pression .
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Aim Using chronic pre-pregnancy stress to establish a postpartum depression animal model, given a single YG,and acute ketamine was served as control, to explore the pathology of PPD and the anti-depressive mechanism of the YG on the PPD model on AKT/mTOR signaling pathway. Methods Thirty-two fe-male Balb / c were randomly assigned to two groups, the control group ( Control, Con) and the pre-pregnancy stressed group(Model,Mod) , which was subjected to 3 weeks chronic restraint stress. After the last stressor, the pre-pregnancy stressed group was housed with a male. After about 4 weeks later, the mice gave birth to pups. Then at 3 weeks postpartum, we tested the ma-ternal tail suspension test ( TST). Both YG and Ket-amine was single administered 24 hours before behavior test, with single saline for control group and PPD mod-el group. After TST,the mouse hippocampus were ex-tracted to detect the expression of AKT and mTOR. Results After 3 weeks postpartum, the model mice showed depression-like behaviors. Immobility in TST was significantly increased in vehicle groups(P <0. 01). Acute YG improved performance in the TST (P< 0. 01), which was similar to ketamine. And the PPD model mice group showed decreased phosphorylation of AKT and mTOR (P < 0. 01,P < 0. 01), compared to control group. A single dose of YG or ketamine normal-ized AKT/ mTOR signaling in the PPD model mice(P< 0. 01,P < 0. 01),( P < 0. 01,P < 0. 01). Conclu-sions Chronic pre-pregnancy stress can induce dams into postpartum depression and its mechanism maybe associated with down-regulating AKT/ mTOR signa-ling. Acute YG exerts fast antidepressant effect on this PPD model similar to ketamine, and its mechanism may be related to up-regulating AKT/ mTOR signaling in the hippocampus.
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Aim To establish a postpartum depression animal model,assess the abnormal maternal behaviors of depressive dams,and observe the rapid antidepres-sant effects of the Yuejuganmaidazaotang (YG)on the PPD model.Methods Thirty-two female Balb /c were randomly assigned to two groups,the control group (Control,con)and the pre-pregnancy stressed group (Vehicle,veh),and vehicle was subjected to 3 weeks chronic restraint stress.After the last stressor,the pre-pregnancy stressed group was housed with a male.Af-ter about 4 weeks later,the mice gave birth to pups. Then at 3 weeks postpartum,we tested the maternal depressive-like behaviors,including sucrose preference test,forced swimming test and novelty suppressed feeding test.Both YG and Ketamine were single ad-ministered 24 hours before behavior test,with single saline for control group and PPD model group.Results After 3 weeks postpartum,the vehicle mice showed depression-like behaviors.Reduced preference in drinking sucrose solution was found in SPT (P <0.01 ).Immobility in FST was significantly increased in vehicle groups (P <0.01 ).In NSFT,the vehicle group displayed a significantly increased latency and reduced unit of food intake compared with control group(P <0.01,P <0.01 ).Acute YG improved per-formance in the SPT(P <0.01),FST (P <0.01)and NSF (P <0.01,P <0.01),which was similar to ket-amine.Conclusions Chronic pre-pregnancy stress can induce dams into postpartum depression.Acute YG exert fast antidepressant effect on this PPD model simi-lar to ketamine.
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Abstact:Aim To identify whether the petroleum e-ther fraction of Yueju pill (YJ-PE)could exhibit a po-tent rapid antidepressant effect and to investigate the underlying biological mechanism involved.Methods Fourty-four male KM mice were randomly assigned to five groups:the control group (saline group),low dosage of YJ-PE,middle dosage of YJ-PE,high dos-age of YJ-PE and ketamine.After a single drug admin-istration,we used tail suspension test (TST)to test the rapid antidepressant effect of YJ-PE in KMmice at 30 min.Another twenty-four male KM mice were ass-inged to three groups:control group,screened effective low dosage of YJ-PE group and ketamine group.We usd TST to assess these mice at 24 h post a single ad- ministration.Western blot was performed to examine the expression of BDNF and TrkB in hippocampus of KMmice at 30 min and 24 h post a single administra-tion.Results An acute administration of YJ-PE de-creased the immobility time of KMmice in TST and in-creased the expression of BDNF and TrkB as soon as 30min post a single administration and lasted at least for 24 hours.Conclusion YJ-PE (low dosage)ex-hibits a rapid antidepressant-like potent,and the po-tent rapid antidepressant effects of YJ-PE are associat-ed with the up-regulation of BDNF and TrkB.