The Effect Of Ginsenoside Re On Reserpine-induced Depression-like Behavior And Its Mechanism

Research background:Depression is a common mental illness,often accompanied by low mood,slow thinking,decreased volition,cognitive impairment,and physical symptoms.Many antidepressants are developed based on the monoamine hypothesis,but these drugs are slow to take effect and have many side effects.Therefore,there is a need to develop more effective antidepressant drugs.Studies have shown that ginsenoside Re has a high content in ginseng and is easy to extract,separate and purify.In addition,ginsenoside Re is one of the main bioactive substances in ginseng,and ginsenoside Re can protective cardiovascular system and nervous system.However,few studies have explored the antidepressant-like effect of ginsenoside Re and its mechanism.Therefore,this study aims to explore the antidepressant-like effect of ginsenoside Re and its mechanism by using the depression animals model induced by reserpine.Methods:Reserpine was administered repeatedly for 7 days to construct a depression model,and then behavioral pharmacology experiments(open field test,forced swimming test,tail suspension test)were used to examine the effects of repeated administration of ginsenoside Re for 7 days on the depression-like behavior.Western blot were used to investigate the effects of repeated administration of ginsenoside Re for 7 days on the expression of depression-related signaling pathway proteins(mTOR,TrkB,BDNF,CREB,and Akt).Furthermore,we used behavioral pharmacology experiments(open field test,forced swimming test,tail suspension test,Y maze)to examine the effect of repeated administration of ginsenoside Re for 14 days on depression-like behavior and spatial working memory.Western blot was used to investigate the effect of repeated administration of ginsenoside Re for 14 days on the expression of TrkB protein and BDNF protein.Results:1.Repeated administration of reserpine for 7 days(2 mg/kg,ip)caused ptosis in mice(p<0.0001),decreased the number of acrossing(p<0.0001)and rearing(p<0.01)of mice in the open field test;increased the immobility time of mice in the tail suspension test(p<0.0001)and forced swimming test(p<0.01),decreased hippocampal BDNF protein(p<0.01)and TrkB(p<0.0001)protein expression levels in mice.2.Repeated administration of ginsenoside Re 30 mg/kg for 7 days(ig)had no effect on the spontaneous activity of mice;Repeated administration of ginsenoside Re 30 mg/kg for 7 days reversed the ptosis induced by reserpine in mice(p<0.05).Repeated administration of Re 30 mg/kg for 7 days decreased immobility time of depressive mice(tail suspension test(p<0.05),forced swimming test(p<0.05)).And also,repeated administration of Re 30 mg/kg for 7 days increased TrkB protein expression of hippocampus of depressive mice(p<0.05).3.Repeated administration of ginsenoside Re 30 mg/kg(ig)for 14 days had no effect on the spontaneous activity of mice;Repeated administration of ginsenoside Re 30 mg/kg(ig)for 14 days decreased immobility time of depressive mice in the forced swimming test(p<0.05),and improved the spatial working memory impairment of depressive mice in the Y maze(p<0.05).Conclusion:Repeated administration of reserpine for 7 days induced depression-like behavior in mice,and the intrinsic molecular mechanism was at least partly mediated by the hippocampal BDNF-TrkB signaling pathway.The repeated administration of ginsenoside Re 30 mg/kg for 7 days may show a good antidepressant-like effect by acting on the TrkB protein.Repetitive administration of ginsenoside Re 30 mg/kg for14 days improved the depression-like behavior and working memory impairment induced by reserpine.