Antidepressant-like Effect And Mechanisms Of Notoginsenoside-rg1

Depression is a group of syndromes characterized by notable and persistent mood disorders, which influences 17% of the population in the world. It is the fourth crippled disease, and has brought great harm to sufferers and society. So, it is necessary to investigate the definite pathogenesis and available drugs of depression. Recently, there are many antidepressants used in clinic, most of which are chemosynthesis drugs. Although these antidepressants have good effects, they also cause many toxic effects. Therefore, researching new antidepressants with greater effectiveness and without (or with lower) side effects and drug dependency from traditional herb has drawn people's attention in China and even foreign countries.Notoginsenoside-Rg1 is one of the major bioactive ingredients of traditional Chinese medicine-Notoginseng. By now, many studies have shown that this component has many pharmacological effects, including increasing brain concentration of brain-derived neurotrophic factor of animal, effect against focal cerebral ischemia reperfusion, effect against fatigue and hypoxia, strengthening learning and memory of animal, and so on. So we presume that notoginsenoside-Rg1 may exert antidepressant-like effects. This study consists of two parts. Background: To evaluate the antidepressant-like effect of Notoginsenoside-Rg1.Methods: Adult male Kunming mice(3 weeks, 18～22 g) were used for chronic mild stress (CMS) model, they were randomized into 7 groups with 20 mice per group. Animals in control and model group were administrated with 0.9% normal saline, imipramine hydrochloride was used as positive control drug and four doses of notoginsenoside-Rg1 (2.5, 5, 10 and 20 mg/kg) were used in the experiment, all drugs were solved in 0.9% normal saline and administrated by intraperitoneal (i.p) injection with a volume of 10ml/kg. The CMS procedure lasted for 8 weeks and repeated drug treatment of CMS mice was performed once daily during the last two weeks. Twenty-four hours after the last stressor and drug exposure, the open field test,tail suspension test (TST) and forced swim test (FST) were performed in the morning.Results: The results of the tail suspension test and the forced swim test showed that the CMS model was very successful, the immobility time of the stressed group was 2-3 times higher than the control group. The positive control treatment with imipramine (15 mg/kg) decreased the immobility time in the TST and FST tests of mice significantly to the level of vehicle-treated group. Notoginsenoside-Rg1 (2.5, 5, 10 and 20 mg/kg) also had the similar effect, decreased the immobility time statistically in a dose-dependent manner (P<0.01, respectively). Locomotion of mice were slightly decreased by CMS compared with un-stressed animals, Imipramine and Notoginsenoside-Rg1 at dose of either 20 mg/kg or 10 mg/kg could reverse it, while neither 5 mg/kg nor 2.5 mg/kg of this drug had the same effect.Conclusion: Notoginsenoside-Rg1 had antidepressant effect on mice'behavior between 2.5 to 20 mg/kg. Background: To explore the possible antidepressant mechanisms of notoginsenoside-Rg1. Methods: After 8 weeks of CMS, ten mice in each group were decapitated, hippocampus were separated out and stored at -80℃for use;five animals in each group were decapitated and serum were separated and stored at -20℃, brains were carefully dissected and stored at -80℃for use; the other 3 mice were perfused and the brains were fixed by 4% paraformaldehyde solution at 4℃. Radioimmunoassay (RIA) was used to assay the serum corticosterone level; reverse transcription-polymerase chain reaction (RT-PCR) were applied to observe the mRNA expression of BDNF in hippocampus of mice after CMS; HE stain was applied to observe the morphology of hippocampal neurons; western blotting technology was also used to observe the effect of notoginsenoside-Rg1 on several proteins related to depression.Results: CMS induced the decreasing of mRNA expression of BDNF, Notoginsen- oside-Rg1 significantly reversed BDNF level, especially at doses of 20 and 10mg/kg, similar to Imipramine; The serum corticosterone level was increased in CMS Kunming mice, Notoginsenoside-Rg1, as well as Imipramine, reduced the augmentation; The result of HE stain indicated that notoginsenoside-Rg1 was able to reverse the change of morphology of hippocampal neurons induced by CMS; We also proved that this herb could increase the expression of some proteins related to depression, such as p-ERK, by western-blotting method.Conclusion: Notoginsenoside-Rg1 possessed a certain antidepressant-like effect via down-regulating of serum corticosterone level. In addition, this herb can promote neurogenesis by increasing the expression of neurotrophic factor and p-ERK.