ABSTRACT
OBJECTIVE: In recent years, available evidence from basic and clinical research on Alzheimer disease(AD) suggests that oxidation stress is involved in the occurrence and development of AD, and that antioxidant treatment can improve the intelligence of patients with AD and delay age-dependant cognitive dysfunction. Although results of basic and clinical research on the therapeutic effects of antioxidants on AD are inconsistent, a large number of available data suggest that these studies are of significance. Basic pharmacological studies on natural antioxidant TA99 series indicate that they are promising novel drugs for AD. Thereby, this study made a review of their experimental basis in the treatment of AD and existing problems.DATA SOURCES: Related articles published between January 1991 and December 2004 were searched by the computer in Medline database with such key words as Alzheimer disease, antioxidant, Ginkgo biloba extract, TA9901,acetylcholine, and senescence-accelerated mouse in different combinations and with the language limited to English. Meanwhile, related articles were alsosearched in CDMA \Wanfang database with the same key words in Chinese.STUDY SELECTION: Literature involving intervention group and control group were screened in the first trial, and then non-randomized trials were excluded and the rest were searched for the full text.DATA EXTRACTION: Of the 24 basic and clinical randomized and non-randomized trials on antioxidants in the treatment of AD collected, 17 accorded with the inclusion criteria and the other 7 were excluded.DATA SYNTHESIS: Intervention in the 17 trials emphasized the pathogenesis of AD from amyloid β proterin(Aβ) synthesis, gathering to senile plaque formation, and the enhancement of Aβ gathering and neuronal apoptosis by peroxidative injuries of free radicals. Both in vitro and in vivo studies were conducted: the effect of Aβ on neurons of different regions was observed with cell culture; transmission electromicroscope and sulfrin T (Th-T) fluorescence assay, Fuliye-transform infrared(FT-IR) spectrum apparatus, electron magnetic resonance(EPR), and round spectrum were used to detect the inhibitory effect of TA99 series on Aβ gathering and fibroplasia in vitro, as well as the influence on Aβ gathering in vivo. Senescence accelerated mouse (SAM) -P/8 was adopted to establish AD model and behavioral studies such as Morris water maze were used to investigate their effect on learning and memory. Meanwhile, the clearance of intracerebral amyloid granular deposition due to TA99 was also observed with hexamic argent staining. The effects of TA series on Aβ target and possible mechanism were fully revealed, and basic pre-clinical data collection was almost completed.CONCLUSION: TA9901 plant extractions have been proved to inhibit Aβ gathering and fibrosis, and improve learning and memory of SAM-P/8 rats. Moreover, TA9902 prepared by TA9901 combined with EGb761, another synergic herb, has an obvious anti-neurotoxic effect by inhibiting Aβ gathering, fibrosis and secondary structural changes. Further pharmacological research is needed and will have a promising prospect.