Antidepressant Effects And Mechanisms Of Schisandra Chinensis And Related Compound Medicine JWYQS

Schisandra chinensis(Turcz.)Baill.as a Chinese functional food,has been widely used in neurological disorders,including insomnia.To explore the antidepressant effect and the underlying mechanisms of Schisandra Chinensis extracts and its major components(SCE,StA,Sch B,Sch A,SCH),relative Chinese herbal compound JWYQS,the present study has been designed to make further explorations on the antidepressant mechanisms of JWYQS.(1)The forced swimming test(FST)and tail suspension test(TST)in mice were used to evaluate the antidepressant activity of SCE,StA,Sch B,Sch A,SCH following single administration intragastrically,and the locomotor activity was investigated to exclude its neural excitatory effects.Effects of SCE,StA,Sch B,Sch A,SCH on neural monoamine systems were studied in two pharmacological models,including 5-HTP induced head-twitches test and yohimbine toxicity potentiation test.(2)To evaluate the antidepressant activity of JWYQS,we used multiple classic depression models,including the FST,the TST,and the learned helpless(LH)test in mice.We investigated the effect of JWYQS on monoamine neurotransmitters using four pharmacological models,including 5-HTP induced head-twitches test,yohimbine toxicity potentiation test,PCPA antagonism experiment and reserpine induced monoamine depletion test;we also used HPLC-ECD to test the level of monoamine neurotransmitters and their metabolite in hippocampus,hypothalamus and prefrontal cortex of reserpine induced mice.We investigated the effect of JWYQS on neurogenesis factors,including the expression of BDNF,and MEK-ERK-CREB signaling pathway in the hippocampus of the LH mice using western blotting.We investigated the effect of JWYQS on inflammatory factors and AKT/NF-?B signaling pathway in the hippocampus of the LPS induced experimental in mice.(1)In behavioral despair models,compared with normal control group,SCE,StA,Sch B,SCH significantly decreased the immobility time in the TST and SCE,Sch B,Sch A,SCH significantly decreased the immobility time in the FST;results of the locomotor activity experiment showed that SCE,StA,Sch B,Sch A,SCH had no excitatory or inhibitory actions on the central nervous system.In the 5-HTP induced head-twitches test,only SCH(10 mg·kg-1)could significantly increased the number of head twitches;SCE,StA,Sch B,Sch A,SCH did not increase the lethality caused by subcutaneous injection of yohimbine at the threshold lethal dosage.(2)In behavioral despair models,compared with normal control group,JWYQS(100?200 mg·kg-1)significantly decreased the immobility time in the TST and FST;results of the locomotor activity experiment showed that JWYQS had no excitatory or inhibitory actions on the central nervous system;In LH test,the results demonstrated that the escape latency and the number of escape failures in mice were significantly reduced after oral administration of JWYQS(50?200 mg·kg-1).In 5-HTP induced head-twitches test,JWYQS(100,200 mg·kg-1)could significantly increased the number of head twitches.JWYQS did not increase the lethality caused by subcutaneous injection of yohimbine at the threshold lethal dosage.JWYQS(100,200 mg·kg-1)could reverse the increase of immobility time in FST caused by intraperitoneal injection of PCPA.In the reserpine reversal experiment,compared with model group,JWYQS(100,200 mg·kg-1)antagonized the palpebral ptosis caused by reserpine(2.5mg·kg-1)treatment,whereas the antagonistic effect did not work when it came to the decreased anal temperature and akinesia symptoms,furthermore,JWYQS could decrease the level of 5-HIAA and 5-HT metabolic rate 5-HIAA/5-HT.In the LH test,compared with inescapable shock mice,the expression of BDNF,TrkB,p-ERK,p-CREB and p-GSK3? was signifisantly increased after oral administration of JWYQS(50?200 mg·kg-1).In the LPS induced depression model,JWYQS(50?200 mg·kg-1)significantly decreased the immobility time in the TST and FST,and increased the preference of sucrose water.In the LH test,JWYQS(50?200 mg·kg-1)reduced the pro-inflammatory cytokine(IL-1?,IL-10)levels and improved the anti-inflammatory cytokine(IL-4)level in model group;In the LPS induced test,JWYQS(50?200 mg·kg-1)reduced the pro-inflammatory cytokine(IL-1?,TNF-?)levels in model group;compared with LPS mice,the expression of p-AKT was significantly increased with NF-?B levels' significantly decreasing after oral administration of JWYQS(50?200 mg·kg-1).Conclusion:(1)SCE,StA,Sch B,Sch A,SCH exerts potential antidepressant-like effects in mice and the underlying mechanisms may be associated with the enhancement of 5-HTergic function induced by SCH.(2)JWYQS has significant antidepressant-like effect in a variety of animal models of depression,the underlying mechanisms may be associated with the regulation of 5-HTergic function,neurotrophic factors and neuroinfammation.