Anti-fatigue Constituents And Mechanism Of Acanthopanacis Senticosi Radix Et Rhizoma Seu Caulis

With the quickening pace of society, long-term work stress and competitive pressure, fatigue is easily happened in working crowd. Fatigue according to different attributes can be divided into two categories:physiological fatigue and pathological fatigue. The former one can be eased through the normal rest, but can not by pathological fatigue. The pathological fatigue has seriously affected the daily life and work, which need to ask for medication or psychotherapy treatment. If fatigue was not alleviated for a long time, it will aggravate to chronic fatigue syndrome (CFS), severe maybe even sudden death. Epidemiological investigations revealed that fatigue occurs in the highly educated, middle-aged people, mostly women, and there is a trend towards the development of young people, which has become one of the major problems of human health in the 21st century. Therefore, development of anti-fatigue drugs has both real meaning and social significance. The clinical medicine for fatigue treatment is mostly the stimulant agents. With addiction and dependence, thus there is substancial limiting its clinical application. Eleutherococcus senticosus was used widely in athletes of the former Soviet Union, since its abilitiy to increase endurance led athletes to good performance in Olypic games. Moreover, the astronauts was also adopted it to prevent stress-related illness. That is why it attracted a lot of attention. However, the active ingredients in the eleutherococcus senticosus against fatigue and the related anti-fatigue mechanism are not yet elucidated.In this study, we used the methods of bioactivity fractionation and gradually tracking. Finaly bioactive compounds were isolated from Acanthopanax senticosus. Further, its pharmacodynamic on attenuating fatigue and the possible mechanism are investigated. Specifically, the root and stem of Acanthopanax senticosus were extracted with 75% ethanol aqueous twice under reflux, followed by partitioned successively with petroleum ether, ethyl acetate, n-butanol. Each fraction was evaporated in vacuo to yield the residues. Then, the weight-loaded swimming test in mice was taken for each fraction administration. The serum urea nitrogen (BUN), triglyceride (TG) and lactate dehydrogenase (LDH) were used as evaluation index for screening the anti-fatigue effect of different frations. After comparision, the petroleum ether and butanol fractions have a good anti-fatigue effect. The chemical analysis of the petroleum ether fraction was adopted by GC/MS and the dominant components were found to be fatty acids. However, n-butanol fraction was fractionation by the prepared D101 macroporous resin in order for the enrichment and purification of active ingredients. After that, the same pharmacological test was used to screen the bioactive fractions eluate from D101 macroporous resin. Eight compounds were isolated and identified in this fraction; most of them were phenolic glycosides.The eleutherosides and eleutheroside E were evaluated for the effects against central fatigue. "Flower pot technique" of sleep deprivation in mice was used as animal model of central fatigue. The behavior alternations after sleep deprivation were adopted as the evaluation of mental fatigue. The hippocampus was harvested after the behavior tests to detect the monoamine levels as well as the oxidative stress. We observed that after sleep deprivation in mice for 24h,48h and 72h, the performace in Y-maze accuracy, the latency to enter the dark chamber of a passive avoidance apparatus and the locomotor activity were impaired significantly as compare to the control (p<0.05, p<0.01), while the behavioral impairment of the mice treated with eleutherosides and eleutheroside E can be significantly improved. Biochemical indexes in hippocampus of mice showed that the mechanism of central fatigue resistance is to increase antioxidant capacity and regulation of serotonin and dopamine levels. Eletherosides have also been found to be a potential antioxidant agency in vitro. Moreover, acute toxicity test showed that the maximum amount of eleutherosides used is approximately 124 times dosage of the Acanthopanax senticosus in clinical.In conclusion, pharmacodynamic results revealed that the eleutherosides has both effects on physical and mental fatigue. Eleutheroside E has the same pharmacodynamic efficacy as well. Therefore, eleutheoside E could be a potential prospect antifatigue substance worthing for clinical study.