Antidepressant Effect Of Total Flavonoids From Lycium Barbarum Leaves On Mice Model Of Depression

Objective:The aim of present study was to investigate the antidepressant effect and possible mechanism of total flavonoids from Lycium barbarum leaves, through establishing behavior despair model and chronic unpredictable mild stress model and to provide reference for its application as pharmacological antidepressant drugs.Methods:1. The forced swimming test (FST) and tail suspension test (TST) were conducted to evaluate the antidepressant effect of total flavonoids from Lycium barbarum leaves. And the open-field test was applied to observe the effect of the total flavonoids extract on automatic activities in mice.2. The unpredictable chronic mild stress (CUMS) model was established, in which mouse were exposed to chronic stress and were given treatment with total flavonoids from Lycium barbarum leaves continuously for 4 weeks. The changes in mouse behavior were used to evaluate curative effect of total flavonoids on the depressive-like mouse.3. SOD activity and MDA content in serum and brain tissue of mouse and NO content in brain tissue of CUMS mouse were measured, to investigate the antioxidant effect of total flavonoids from Lycium barbarum leaves.4. Morphological changes of hippocampal neurons were observed and the number of expressing BDNF positive cells in prefrontal cortex were measured, to evaluate the neuron protective effect of the total flavonoids.Results:1. The Immobility time of FST was significantly reduced by the dose of 30 mg/kg,100 mg/kg and 300 mg/kg of total flavonoids extract by intragastric administration for 14 d continuously in mouse. Similarly, the immobility time of TST was significantly decreased by the dose of 100 mg/kg and 300 mg/kg of the extract. Little effect on the automatic activities was found in the open-field test at the three dose levels compared with the control group.2. Compared with the control group mouse, the weight, the degree of preference for sucrose and the automatic activities of stressed mouse were lower after exposed to chronic stress for 2 weeks. After administration with total flavonoids from Lycium barbarum leaves continuously for 4 weeks, the weight of the total flavonoids group mouse were higher than the model group but lower than the control group; each dose of 300 mg/kg,100 mg/kg and 30 mg/kg of total flavonoids can improve the sucrose preference degree and there was significant difference compared with the model group (P<0.05); three kinds of dose of total flavonoids can improve the automatic activities of stressed mouse, and the dose of 100 mg/kg,300 mg/kg produced significant effect (P<0.05, P<0.01); the dose of 300 mg/kg significantly reduced the immobility time of FST and TST compared with the model group (P<0.05).3. SOD activity in serum and brain tissue of mice was significantly increased following treatment for 14 d continuously, while MDA content in serum and brain tissue of mouse was significantly decreased in the behavior despair model test. While in the CUMS model, SOD activity in serum was significantly increased by the dose of 30 mg/kg and 300 mg/kg, and MDA content in serum was significantly decreased by all three kinds of dose of the total flavonoids (P<0.05, P<0.01); the dose of 100 mg/kg and 300 mg/kg decreased the NO content in brain tissue compared with the model group.4. The total flavonoids can maintain the morphology of neurons in the hippocampal CA3 region and the neuron cell atrophy was inhibited by the total flavonoids; the total flavonoids increased the expression level of BDNF in prefrontal cortex.Conclusion:The total flavonoids from Lycium barbarum leaves has antidepressant activity, and can alleviate the abnormal behavior of depressed mouse. The mechanism of antidepressant effect of the total flavonoids may be associated with its antioxidant activity, increasing the expression level of BDNF and effect of neural protection.