Antidepressant Effects Of Bioactive Compounds From Entomogenous Fungi And Its Mechanisms

Depression is an affective disorder,it has muiti-negative influences to personal, family and society. The incidence of depression is rapidly increasing these years.Depression is an complicated disease,it is foun that depression is related with heredity, neuromediums and with body, psycologicol factors and circumstance. There have no satisfactory drugs to therapy depression so far. BCEF is a new type of bioactive compounds from entomogenous fungi. It's found that it has inhibition effect on monoamine oxidase and it's also an effective free radical scavenger. So,BCEF is an latent antidepressant.Our research studied the antidepressant effects of bioactive compounds from entomogenous fungi and its possible mechanisms by using methods in vivo and in vitro in body,celluar, molecular and gene levels.The main results are as follows:1 Acute toxicity of BCEFAfter administration large dose of BCEF by ig and ip, the mouse appeared sedation and crimple and the diet is decreased.Some animals appeared opisthotonus symptom. The caculation resuits of LD50 using Bliss method 7ds later are as follows:LD50(ig)=3169.5mg kg-1, A=-30.30, B=11.15;LD50(ip)=1461.65mg kg-1, A=-20.94, B=7.41.Compared with effective dosage (12.5 ~ 150 mg kg-1) , the acute toxicity of BCEF is low and it's an security agent.2 Effect of BCEF on arecaline induced dindling response in mouseAfter administration arecaline (ip,0.1 mg kg-1), All group mouse revealed thrill -ling response, excluding atropine group. BCEF has no effect on dindling latent period and dindling duration and atropine can shortting the dindling duration by recaline admin -istra tion. So, the results showed that has no anti-effect to dindling response by arecali -ne and it also showed that BCEF has no antiacetylcholinergic effect.3 Effect of BCEF on spontaneous activity (upright activity and aclinic act i v i ty) i n mouseThe results showed that BCEF12.5, 25, 50 mg kg-1 could not alter the number of upright activities and aclinic activities.It showed that BCEF(12.5, 25, 50 mg kg-1, ig,qdx 14d) has no effect on spontaneous activity in mouse.4 Antidepressant effect of BCEFThe antidepressant effect of BCEF was studied on drugs induced models, behav -ioral despair models, chronic unpredictable stress models and separated model. 4. 1 Drugs induced modelsReserpine reversal test, yohimbine induced lethality test, apomophine induced stereotyped behavior test and 5-HTP induced head-twitches test were used. The results are as follows:After administration reserpine (sc,2.5 mg kg-1), the rats and mouse appeared physical signs such as body bowing, laxing hairs, blepharoptosis and akinesia. Chronic precautionary administratiof BCEF(25, 50, 100 mg kg-1, ig,qdx14d)could notaltered the scores of blepharoptosis and akinesia, but could distinctively step-up the decreasing body temperature in rats. Chronic remedial administratiof BCEF(25, 50, 100 mg kg-1, ig,qdxl4d) could obviously inhibite the blepharoptosis and akinesia and it appeared some extent of dose-effect relationship. These results showed that BCEF could enhance the function of monoamine transmitters system in some degree.After administration yohimbine (sc,30mg kg-1) about 10 minutes or so, each group mice presented intoxication response such as stiffing muscle, livor skin and difficulty in activity, et al. After administration yohimbine half an hour, BCEF100mg kg-1 group mice began died. After administration yohimbine 1 hour, BCEF25, 50, 100mg kg-1 group mice mortality rate rising rapidly. After administration yohimbine 2 hour, 5 hour 24 hour, there was no difference among each group. These results showed that BCEF could enhance the function of NE nerves system in some degree.After administration 5-HTP (ip,100mg kg-1) 2 or 3 minutes, each group mice presented head-twitch response. The top frequency approximate in 5-20 5-HTP and it last to 90 minutes after administration. BCEF(50, 100mg kg-1) could distinctly increase the head-twitch number. These results showed...