Antidepressant Effect And Possible Mechanisms Of Bioactive Compounds From Entomogenous Fungi (BCEF0083)

BCEF0083 is a new type of bioactive compounds from Entomogenous fungi, which acts both as an inhibitor of monoamine oxidase and an effctive free radical scavenger. In our former studies, we have found BCEF0083 possesses antidepressant effect on different animal models. Based on these foundations, this study is intended to further investigate the antidepressant effect and possible mechanisms of BCEF0083 in chronic unpredictable stress rat model. The main results are as follows:1. Effect of BCEF0083 on behaviour in open-field test and consumption of saccharu water in chronic stressed ratsThe model was induced by giving the rats different unpredictable stresses in 21days. The behavior was tested in open-field test. We detected animal's awarding response by calculating the 24hour consumption of saccharu water.BCEF0083(25,50mg kg-1,ig,qdx21d) could increase ambulation and rearing score in chronic stressed rats in open-field test.BCEF0083(25,50,100mg kg-1,ig,qdx21d) could increase 24hour consumption of saccharu water and ameliate animal's awarding response .2. Effect of BCEF0083 on sleep-weekfulness cycle in chronic stressed ratsStereotaxic and polysomnography were used to record the sleep-wakefulness cycle.BCEF0083 50mg kg-1ig, qdx21d) could attenuate REMS percent in chronic stressed rats. BCEF0083 (25,50,100 mg kg-1,ig,qdx21d) could prolong REMS latency in chronic stressed rats.The results suggested that BCEF0083 could ameliate abnormal sleep-wakefulness in chronic stressed rats.3. Effect of BCEF0083 on lipid peroxidation in chronic stressed ratsUV spectrophotometer analysis technique was used to detect the SOD, GSH-PXactivity and MDA content.BCEF0083(25,50,100 mg kg-1,ig,qdx21d) could enhance the activities of SOD,GSH-PX and decrease the content of MDA in chronic stressed rats.4. Effect of BCEF0083 on Hypothalamic-pituitary-adrenal axis in chronic stressed ratsRadio-immunity analysis technique was used to detect the content of AVP. Semi-quantitative RT-PCR technique was used to detect the GR mRNA.BCEF0083(25,50,100mg kg-1,ig,qdx21d) could decrease the content of AVP in hypothalamus and pituitary in chronic stressed rats. BCEF0083(50,100 mg kg-1, ig, qdx21d) could enhance the expression of GR mRNA in hippocampus in chronicstressed rats.5. Effect of BCEF0083 on hippocampus neuron in chronic stressed ratsHE staining, immunohistochemistry and Semi-quantitative RT-PCR technique were used.BCEF0083(25,50mgxkg-1,ig,qdx21d) could increase the numbers and content of BDNF in hippocampus neuron in chronic stressed rats. BCEF0083(50, 100mg kg-1, ig, qdx21d) could increase expression of BDNF mRNA in hippocampus neuron in chronic stressed rats.Conclusions: BCEF0083 could increase ambulation as well as rearing score in open-field test, 24hour consumption of saccharu water in chronic stressed rats and ameliate abnormal sleep-wakefulness in chronic stressed rats. The result of this study suggested that BCEF0083 possess certain antidepressant effect. The possible mechanisms might be attribute to anti-lipid peroxidation, restore the disorder of HPA , accelerate the nutrition and regeneration of hippocampus neuron.