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


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.
Sichuan Medical University, Luzhou 646000, China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Wang
W
Qiong
School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China; National Laboratory of Human Factors Engineering / the State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
Zhang
Z
Yong-Liang
School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China; National Laboratory of Human Factors Engineering / the State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
Li
L
Ying-Hui
National Laboratory of Human Factors Engineering / the State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China.
Chen
C
Shan-Guang
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Gao
G
Jiang-Hui
Sichuan Medical University, Luzhou 646000, China.
Chen
C
Yi-Xi
Sichuan Medical University, Luzhou 646000, China.
Jiang
J
Ning
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; National Laboratory of Human Factors Engineering / the State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China. Electronic address: liuxinmin@hotmail.com.
Liu
L
Xin-Min
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004924:Escape Reaction / Q000187:drug effects; D019417:Hindlimb Suspension; D008297:Male; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood; D013550:Swimming; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014893:Weightlessness / Q000009:adverse effects*
D004365:Drugs, Chinese Herbal; C000605449:Kai-Xin-San; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D003849:Deoxyguanosine
Antioxidant; Cognitive deficit; HLS; KXS; Simulated weightlessness