Effects And Mechanisms Of Chinese Herbal Compound-Q0409 Preventing And Curing The Inability In Learning And Memory

The inability of learning and memory usually occurs in the process of Alzheimer’s disease （AD） and Vascular dementia （VD）. It is an important question in medicine science to improve the ability of learning and memory and treat dementia. New compound Q0409 of Chinese herbs （CH-Q0409）, which is composed under the direction of Chinese Medicine theories, improved the abilities of learning and memory in the mice of the impaired learning and memory. To reduce the compositions and enhance the therapeutic effects, we are determined to sieve the CH-Q0409 and investigate the pharmacodynamics and the related mechanisms.The studies were divided into following five parts:Part 1～2: To sieve the CH-Q0409 by the ethological paramemters and neurobiochemical indicator （true cholinesterase, TchE） in orthogonal design, and then to verify the simplified CH-Q0409’s effects of improving the learning and memory in the mice of the impaired learning and memory induced scopolamine. The results showed that the sconfirmed and simplified CH-Q0409 only was composed of two Chinese herbs （Radix Polygalae and Radix Ginseng）. The optimized dosage was also confirmed by the verified-design experiments. （China patent applied№200710027878.4）Part.3: Senescence accelerated-prone/8 mice （SAM-P/8）, which was 4 months old, were treated by the simplified CH-Q0409 （SCH-Q0409, be from Part 1～2） for 60d. The records of learning and memory, the activities of TchE, the changes of morphology （immunohistochemistry and ultramicrostructure） and the 113 genes expression of neurotophin and apoptosis etc. were determined. At the same time, huperzine A was selected as the control drug to compare the therapeutic effects. The findings suggested that the SCH-Q0409 had the therapeutic effects in AD. Except that the parameters of ethology and the morphology in SCH-Q0409 group is better than that in huperzine A group, the3 other parameters is similar to each other. The mechanism of SCH-0409 were related to inhibit the activities of TchE in hippocampus of mice, to reduce the proteinosis of amyloidβprotein （Aβprotein）, to protect mitochondrial ultramicrostructure and to inhibit the apoptotic genes expression. （Be applying patent.）Part 4: The high performance liquid chromatography/diode array detector （HPLC/ DAD） and high performance liquid chromatography/tandem mass spectrometry （HPLC/MS/MS） were applied in determining the major monomers of SCH-Q0409 （be from Part 1～3）. The results demonstrated that the major monomers of SCH-Q0409, which is ginsenoside Rg1, Rb1, Re and presenegenin, were absorbed into the blood in mice. The average drug levels of the major monomers was calculated and were the reference data in mechanism study of SCH-Q0409 in the disease’s cellular model in vitro.Part 5: AD cellular model was established by PC12 cells induced by nerve growth factor （NGF） and injured by Aβprotein. The major monomer compound of SCH-Q0409 （be from Part 5） was observed the effects on the AD cellular model. Orthogonal design was again to use in finding the optimizated compatibility and concentration of the major monomer compound （MMC）. The results showed that the MMC protect PC12 from apoptosis induce Aβprotein. The further findings demonstrated that MMC reduce the apoptotic rate, which was also verified by Hoechst staining. Moreover, the mechanism of MMC’s neuroprotective effect on AD cellular model related to that MMC inhibited the decline of mitochondrial membrane potential （DiOC₆（3） flow cytometry） and maintain the mitochondrial quality （NAO flow cytometry）. （China patent applied№200710027621.9）To summary all of strateoies in these experiments: In the system-studies of the Chinese herbal compound （CHC）, optimizated （gold） disease’s model, direction of appropriate mathematics mode, sufficient preparation in references and contemporary advanced science and technology （like finger print of Chinese herb, gene chip, many sciences cooperation required） will help us sieve and confirm the CHC or MMC quickly and efficiently. Furthermore, the protection of intellectual property rights is important for the every researchers.In summary, our studies provided the research data in theory and practice to improve the abilities in learning and memory. It also can apply to Chinese herb’s research in preventing and curing the impaired learning and memory and dementia.