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Based On The BDNF Related Signal Transduction Pathwaysin Study The Mechanism Of The Antidepressant Effect Of Flavonoids Of Glycyrrhiza Uralensis

Posted on:2014-05-07Degree:MasterType:Thesis
Country:ChinaCandidate:J GuoFull Text:PDF
GTID:2334330479982096Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective: To study the antidepressant effect of the flavonoids extract parts(Licorice flavonoids, LF) from Glycyrrhiza uralensis in chronic unpredictable stress rat model.Method: 60 male Sprague-Dawley(SD) rats were randomly assigned into 6 groups as control, model(stress+vehicle, ig), fluoxetine group(stress+fluoxetine 3.5 mg/kg, ig) and 3 LF groups(stress + LF 30, 100, 300 mg/kg, ig). All rats were exposed to chronic unpredictable stress(CUS) for 28 consecutive days. At the end of the experiment, after the weight detection, we applied the Forced Swimming Test, Open Field Test and the Tail Suspension Test to assess the antidepressant efficacy, and we still measured the serum corticosterone(CORT) level by radio immunoassay method.Result: The flavonoids extracted parts from Glycyrrhiza uralensis can significantly short the motionless time in Forced Swimming Test(P<0.05 or P<0.01) and in Tail Suspension Test(P<0.05 or P<0.01). In the Open Field Test, the flavonoids can improved the stress behavior performance by increasing rearing times(P<0.05 or P<0.01) and the horizontal crossing numbers(P<0.01),and by decreasing the number of fecal produced(P<0.01). Still, the 300mg/kg dosage of flavonoids can significantly lower the serum corticosterone level in CUS rats(P<0.01).Conclusion: The flavonoids extracted parts from Glycyrrhiza uralensis showed the antidepressant effect on CUS rats.Objective:To study the antidepressant effect of the Licorice flavonoids(LF) from Glycyrrhiza uralensis, the chronic unpredictable stress model was employed to evaluate the effect by animal behavior research and blood biochemical experiments to observe time-effective relationship of LF. And the immunohistochemical, molecular biology, western blot and biochemical techniques were used to exploring the antidepressive mechanism in relationships associated with the BDNF signaling pathway and its receptor Trk B.Method:72 male Sprague-Dawley(SD) rats were randomly assigned into 6 groups as control, model(stress + vehicle, ig),fluoxetine control group(stress + fluoxetine 10 mg/kg, ig),LF groups(stress + LF 100, 300 mg/kg, ig) and LF maximum dose control group( 300+, 300 mg/kg dosage of LF by intragastric administration without stress). Chronic unpredictable stress(CUS) was carried out for 28 consecutive days,and the body weight gain measurement, forced swimming test, open field test and tail suspension test were applied weekly to assess the antidepressant efficacy and related timetable as well. At the end of the experiment, all rats were anaesthetized with ethyl carbamate(1.4g/kg, ip) for specimen collection. The serum BDNF level was measured by ELISA method. The changes of the BDNF,Trk B and p Trk B protein expression in hippocampus were examined by immunohistochemistry approaches. We still employed western blot to monitor the BDNF content changes in hippocampus and the Quantitative real-time PCR analysis for m RNA expression of the BDNF and Trk B.Result: 1. The effect result of the body weight gain: Compared with the model group,Flavonoids can increase body weight(P<0.05 or P<0.01)after 28 days of consecutive stress except the 300+ group(P>0.05).2. The result of behavioral test: The flavonoids can significantly short the motionless time in Forced Swimming Test(P<0.05 or P<0.01) and in Tail Suspension Test(P<0.05 or P<0.01). In the Open Field Test, the flavonoids can improved the stress behavior performance by increasing rearing times(P<0.05 or P<0.01),grooming time(P<0.05 or P<0.01) and the horizontal crossing numbers(P<0.01),and by decreasing the number of fecal produced(P<0.01).3. Result in serologic index : Compared with the normal group, the BDNF serum levels decreased significantly(P <0.01) in the model group. The flavonoids can increase the serum BDNF levels((P <0.05 or P <0.01).4. The immunohistochemistry results:(1) Compared with the normal group, BDNF protein expression in cortex regions, CA1 subfield(CA1), CA3 subfield(CA3) and dentate gyrus(DG) of hippocampus were significantly heightened in the flavonoids treated rats(P<0. 05 or P <0.01).(2)Compared with the normal group, Trk B/p Trk B expression in the CA1, CA3, DG and cortex regions were significantly heightened in the flavonoids treated rats(P<0. 05 or P <0.01).5. Western blot results: Compared with the normal group, stress can decreased the BDNF protein expression in hippocampus(P<0.01). High doses of the flavonoids and the positive control drug fluoxetine can improve the level of BDNF protein expression in hippocampus(P <0.05 or P <0.01).6. q PCR results : Compared with the normal group, stress can decreased the BDNF and Trk B m RNA expression level in hippocampus(P<0.01). Flavonoids and fluoxetine can improve the m RNA expression of the BDNF and Trk B in hippocampus(P <0.05 or P <0.01).Conclusion: The flavonoids extracted parts from Glycyrrhiza uralensis may produce the antidepressant effect in chronic unpredictable stress depression model in rat, and its relevant mechanisms may be associated with the increasing BDNF signal transduction pathway.
Keywords/Search Tags:Glycyrrhiza uralensis, flavonoids, stress, depression, corticosterone, Glycyrrhiza uralensis Fisch, BDNF, Trk B
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