Effects of Chinese herbal medicine fuzhisan on aged rats.
Fuzhisan (FZS), a Chinese herbal complex prescription, has been used in the treatment of Alzheimer's disease (AD) for more than 15 years. Previous studies showed that FZS enhanced the cognitive ability in AD patients and AD model rats. FZS modulated the impaired cellular functions, and attenuated the damage caused by beta-amyloid protein, dose-dependently regulated and ameliorated the cholinergic functions of the Abeta(25-35)-induced AD-model mice. The SPECT imaging revealed that FZS improved the blood flow of the frontal and temporal lobes and the callosal gyrus in AD patients. However, little investigation of the effects of FZS on the naturally aged rats was reported. The underlying mechanism also remains to be explored. Recently we investigated the effects of the aqueous extract of FZS on the cognitive functions of the aged rats and the pharmacological basis for its therapeutic efficacy. The results showed a significant improvement made by FZS (0.3, 0.6, and 1.2 g/kg/d) for impaired cognitive functions of the aged rats. The rats manifested a shortened latency in Morris water maze test after intra-gavage administration (ig) of FZS for 30 consecutive days. The micro-positron emission tomography (microPET) using (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) as the tracer demonstrated that FZS promoted the glucose metabolism in the whole brains especially the temporal and parietal regions in the aged rats. The spectrophotometry and Western blot showed that FZS obviously increased the activity and the production of choline O-acetyltransferase (ChAT, EC 2.3.1.6) and the acetylcholine (ACh) contents in the hippocampus, thus regulated and ameliorated the impaired cholinergic functions of the aged rats. The therapeutical effects of FZS on the learning and memory of the aged rats were dose-dependent. The mechanism of action of FZS in ameliorating the memory dysfunction of the aged rats is ascribed to the reinforcement of the function of the cholinergic system and the enhancement of the glucose metabolism in the brains. The results of this study, together with a survey of the findings in the clinical treatment with FZS suggest that FZS may not merely alleviate the symptoms of the dementia, but may also augment the production of the neurotransmitter ACh and the energy supply in the brain to build up fitness of the patients. FZS may be beneficial for the treatment of Alzheimer's disease or cognitive impairment in old people.
Li
Xu Ling
XL
Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Wang
De Sheng
de S
Zhao
Bao Quan
BQ
Li
Qian
Q
Qu
Heng Yan
HY
Zhang
Ting
T
Zhou
Jian Ping
JP
Sun
Man Ji
MJ
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000187:drug effects* / Q000523:psychology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008517:Phytotherapy / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D002795:Choline O-Acetyltransferase; D005947:Glucose; D000109:Acetylcholine