The Research On The Nootropic Characteristics And The Mechanisms Of Four Dammarne Triterpenoid Saponins

A number of studies have shown the damamrane type triterpenoid saponins have the significant effects on improving cognitive function and it is given priority to the protopanaxatriol-type saponins and the protopanaxadiol-type saponins,especially concentrated on the abundant representative components ginsenosides Rgl and ginsenosides Rb1.While the reports about the cognitive effects of their metabolites Rhl,Rh2,PPT and PPD are very limited,and Rgl and Rbl have the different characteristics of the cognitive function.Hence,the research on the characteristics of the cognitive effects and mechanism of the the four triterpenoid saponins will be helpful for better understanding and interpretation of the pharmacological effects of the damamrane type triterpenoid saponins and can provide protective drug for effectively protective measures of cognitive dysfunction.In this paper,the main research contents and results are as follows:1.The protopanaxatriol-type saponin Rhl and the protopanaxadiol-type saponin Rh2 have the different characteristics of the cognitive effects.The effects of Rhl and Rh2 on scopolamine-induced and chronic sleep interrepution-induced cognitive impairment mice models were determined with the open field,object recognition,morris water maze and step-through tests after 20?40?mol/kg of both Rhl and Rh2 were administrated ip for 2 weeks.The results showed that both Rhl and Rh2 can improve the impaired memory performance induced by scopolamine and chronic sleep interrepution in object recognition,morris water maze and step-through tests.It was worth noting that the protopanaxatriol-type Rhl was more effective than the protopanaxadiol-type saponin Rh2 on improving the spatial learning and memory ability,while the protopanaxadiol-type saponin Rh2 showed more active effects than the protopanaxatriol-type Rhl on the short-term memory ability.2.It was firstly found that both PPT and PPD not only have obvious promoting effects on the processes of memory acquisition,consolidation and recall,but also could improve the impaired memory performances caused by chronic sleep interepution.And the characteristics and mechanisms of action were different between PPT and PPD.The memory consolidation and memory recall impairment mice models were established by ip 0.75 mg/kg scopolamine respectively in different stages of object recognition and step-through experiments.The results showed that after 20?40?mol/kg of both PPT and PPD were administrated ip for 2 weeks,both PPT and PPD could improve the impaired memory performance induced by scopolamine and promote the memory acquisition,consolidation and recall processes.In improving acquisition impairment caused by scopolamine,it was interesting to note that PPT was more effective in improving spatial learning and memory ability,while PPD was more active in enhancing short and non-spatial memory ability.The two ginsenosides acted through different mechanisms:PPT exhibited the effects mainly by inhibiting the activities of AchE caused by scopolamine,relieving oxidative stress damage and up-regulating the expressions of CREB and the immediate early gene c-Fos,c-Jun and Egr-1 in hippocampus,While PPD exhibited the effects by increasing ChAT activity caused by scopolamine,declining against oxidative stress damage,adjusting the expressions of c-Fos,and Egr-1 in hippocampus,but not affecting CREB expression and even down-regulating c-Jun expression.The difference in the mechanism of action may explain the difference in the cognitive characteristics.There was no significant difference between PPT and PPD in improving memory consolidation and recall processes.As for the chronic sleep interepution-induced cognitive impairment,both PPT and PPD also showed significant improvements and they had the different cognitive characteristics:PPT was more effective in improving spatial learning and reference memory ability.3.It was confirmed that the metabolite PPT had stronger cognition-enchancing effects than its prototype Rhl and their mechanisms were similar.The efficacy of Rhl and Rhl's metabolite PPT in ameliorating learning and memory impairment had been evaluated in scopolamine-induced and chronic sleep interepution-induced mice models.The results showed that compared with Rhl equivalent dosage,PPT had stronger effects on enhancing the learning and memory ablitiy.And the mechanisms of action were similar.4.It was firstly compared that Rh2 with its metabolite PPD in the cognition-enhancing effects and also verified that the metabolite PPD had the similar and showed stronger effects than Rh2 in memory enhancement.The scopolamine-induced and chronic sleep interepution-induced mice models were applied to evaluate the cognitive effects of Rh2 and Rh2's metabolite PPD.The results demonstrated clearly that both Rh2 and PPD could show the cognition-enhancing effects by regulating cholinergic neurotransmitter and relieving oxidative stress damage and PPD was more active than Rh2.This research paper applied two kinds of learning and memory impariment animal models to study the cognitive function and the characteristics of four darma alkanes type triterpenoid saponins Rh1?Rh2,PPT and PPD from the whole animal behavior,central cholinergic system neurotransmitter,oxidative stress,and learning and memory related signals.The results showed that the protopanaxatriol saponins and protopanaxadiol saponins have different characteristics in improving learning and memory effects and the metabolites are more active than their prototypes.The results can provide theoretical foundation and scientific basis for damamrane type triterpenoid saponins researched on the pathogenesis of complex cognitive impariments related diseases and provides new drug candidates for seeking the effective noontropic drugs.