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OBJECTIVE To explore the antidepressant effect and potential mechanism of icariside Ⅱ （ICSⅡ） based on the GABAergic nervous system. METHODS The male Kunming mice were randomly divided into a control group （group C， 10 mice） and a modeling group （50 mice）. The depression model was induced by chronic unpredictable mild stress （CUMS） method in the modeling group. After 21 days of stimulation， the rats of modeling group were randomly divided into depression model group （NS group）， positive control group [ECS group， oxalate escitalopram 15 mg/（kg·d）] and ICSⅡ low-dose， medium-dose and high-dose groups [ICSⅡ-L group， ICSⅡ-M group， ICSⅡ-H group； ICSⅡ 10， 20， 30 mg/（kg·d）]， with 10 mice in each group. Administration groups were given relevant medicine intragastrically， once a day， for 14 consecutive days. The sugar water preference rate， total exercise distance， immobility time in tail suspension and forced swimming experiments were detected in each group. The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed； the contents of γ-aminobutyric acid （GABA） and glutamic acid （Glu）， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins （GABA A receptor α1， GABA B receptor 1， vesicular GABA transporter， glutamate decarboxylase 67， GABA membranal transporter 3） were detected in hippocampus. RESULTS Compared with group C， the sugar water preference rate and the total exercise distance significantly reduced in NS group， while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged （P＜0.05）. The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced， with a significant decrease in the number of structurally intact neurons （P＜0.05）； the content of Glu was significantly increased， while the content of GABA， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins were significantly decreased （P＜0.05）. Compared with NS group， depression behavior in each administration group was improved， and the above indexes were mostly reversed （P＜0.05）. CONCLUSIONS ICSⅡ can improve depression behavior of depression model mice. The mechanisms may be associated with regulating the balance of GABA and Glu， increasing the synthesis， transport and release of GABA， and regulating the expressions of GABA-related receptors， so as to improve GABAergic nervous system.
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The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,β1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.