Liu Xinmin

The memory enhancement effect of Kai Xin San on cognitive deficit induced by simulated weightlessness in rats.

ETHNOPHARMACOLOGICAL RELEVANCE It is vital for astronauts to develop effective countermeasures to prevent their decline of cognitive performance in microgravity to make space-flight missions successful. The traditional Chinese herbal formula Kai Xin San (KXS) has been used to treat amnesia for thousands years. It is a traditional complex prescription comprising of ginseng (Panax ginseng C. A. Meyer), hoelen (Poria cocos (Schw.) Wolf), polygala (Polygala tenaifolia Willd), and acorus (Acorus tatarinowii Schott). Previous study showed KXS could improve CMS-induced memory impairment in rats. MATERIAL AND METHODS In this paper, a unique environmental factor-microgravity (weightlessness) was simulated as hindlimb suspension (HLS) by tail in rats for two weeks as the HLS animal model. The KXS at the doses of 0.3 or 0.6g/kg p.o. daily was administrated to HLS rats for two weeks at the same time of HLS, the memory behavior tests were investigated with Morris water maze (MWM) and Shuttle Box (SB) test. The levels of ROS, 8-OHdG and 3-nitrotyrosine (3-NT) in the serum, and AChE and ChAT activity in the brain of rats were determined by ELISA or biochemical analysis. RESULTS After HLS for two weeks, the escape latency and the swimming distance were significantly increased in the MWM test in rats in the HLS group, compared with control group. The percent of swimming distance in target quadrant and the number of target crossing was significantly decreased in rats in the HLS group compared with the control group. Performance in the SB test showed, the numbers and the distance of active avoidance was decreased from day 4 to day 7, the time spent in electric area was increased in rats in the HLS group compared with the control group. Administration of KXS 0.3 or 0.6g/kg to the HLS rats for two weeks significantly reduced the escape latency and the swimming distance, increased the percentage of swimming distance in target quadrant and the number of target crossings (P<0.01, compared with the HLS group) in the MWM test. Similar treatment with KXS increased the numbers and the distance of active avoidance (P<0.01, compared with the HLS group) and reduced the time spent in electric area after training 3 days in the SB test (P<0.01, compared with the HLS group). The HLS induced the increase of the ROS, 8-OHdG and 3-NT in the serum of rats, but has little influence on the AChE, ChAT activity in the brain. Only the AChE activity in the cortex and the ChAT activity in the hippocampus had some changes in rats in the HLS model group. After administration of KXS 0.6g/kg for two weeks, the abnormal levels of ROS, 8-OHdG, 3-NT were found reversed in the serum of rats (P<0.05, compared with HLS model group). And KXS 0.3g/kg was found reversed the increased AChE activity in the cortex. CONCLUSIONS Experimental results from this study show that KXS may improve memory deficiency induced by HLS, its mechanisms are major related to antioxidant activities, rather than the central cholinergic system.

Effects of Ginsenoside Rg1 on Learning and Memory in a Reward-directed Instrumental Conditioning Task in Chronic Restraint Stressed Rats.

Ginsenoside Rg1 is one of the major active ingredients of Panax ginseng and has showed notable improving learning and memory effects in several behavioral tasks, such as water maze, shuttle‐box, and step‐through, based on avoidance. However, there was no report about the role of Rg1 on the performance of reward‐directed instrumental conditioning, which could reflect the adaptive capacity to ever‐changing environments. Thus, in this study, the reward devaluation test and conditional visual discrimination task were conducted to study the ameliorating effects of Rg1 on cognitive deficits, especially the loss of adaptation capacity in chronic restraint stress (CRS) rat model. Our results showed that rat subjected to CRS became insensitive to the changes in outcome value, and it significantly harmed the rats performance in conditional visual discrimination task. Moreover, the levels of BDNF, TrkB, and Erk phosphorylation were decreased in the prefrontal cortex of CRS rats. However, these changes were effectively reversed by Rg1 (5 and 10 mg/kg, i.p.). Therefore, it demonstrated that Rg1 has a good ability to improve learning and memory and also ameliorate impaired adaptive capacity induced by CRS. This amelioration effect of Rg1 might be mediated partially by BDNF/TrkB/Erk pathway in prefrontal cortex. Copyright