Ginsenosides attenuate d-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease.
BACKGROUND
Panax ginseng C.A.Mey. is a traditional Chinese herbal medicine, which has been used to treat Alzheimer's disease (AD) for thousands of years. Ginsenoside is one of the major compounds found in P. ginseng. This study aimed to explore the attenuation of spatial memory impairment by ginsenosides and its correlation with restoring the dysfunction of the neurotransmitter systems in AD model rats to understand the mechanism underlying the anti-AD effect of P. ginseng.


METHODS
In this study, the AD model was established by combining d-galactose (d-gal) with AlCl3(Al) for 60 days. From day 30, the ginsenosides group was intragastrically administered with ginsenosides for 30 days. The ethology of rats was tested through the Morris water maze test(MWM). Histopathological changes in the hippocampus of rats were observed through hematoxylin and eosin staining. The expressions of amyloid β peptide (Aβ) and phospho-tau (p-tau) in the hippocampus and cortex of rats were detected by immunohistochemistry. A liquid chromatography-mass spectrometry assay was used to measure neurotransmitter concentrations in the hippocampus, cortex, and blood.


RESULTS
Ginsenosides could significantly decrease the escape latency time and the average latency time in the place navigation test and increase the times of crossing the platform area, the percentage of residence time, and the distance in the original platform quadrant in the spatial probe test. Ginsenosides could repair the damage of the hippocampus and reduce the expressions of Aβ and p-tau. Ginsenosides could also increase γ-aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and aspartic acid levels in the hippocampus and cortex and increase glycine and serotonin levels in the blood.


CONCLUSIONS
After effectively administrated, ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.
National Center for Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; School of Chemical and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, PR China.
Yan
Y
Zhang
National Center for Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: mslab21@ciac.ac.cn.
Zifeng
Z
Pi
National Center for Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Fengrui
F
Song
National Center for Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: liuzq@ciac.ac.cn.
Zhiqiang
Z
Liu
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D005690:Galactose / Q000633:toxicity*; D036145:Ginsenosides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D017607:Aluminum Compounds; D002712:Chlorides; D036145:Ginsenosides; D018377:Neurotransmitter Agents; D000077410:Aluminum Chloride; D005690:Galactose
Acetylcholine (PubChem CID: 187); AlCl(3) (PubChem CID: 24012); Alzheimer's disease; Aspartic acid(PubChem CID: 424); D-Galactose (PubChem CID: 6036); Dopamine (PubChem CID: 65340); Ginsenosides; Glutamate (PubChem CID: 33032); Glycine (PubChem CID: 750); Liquid chromatography–mass spectrometry; Morris water maze; Neurotransmitters; Serotonin (PubChem CID: 5202); γ-aminobutyric acid (PubChem CID: 119)