| With the increase of the aging population, Alzheimer’s disease has become one of the serious health threaten to elderly life in today’s society. AD as a degenerative diseases of the central nervous system(CNS) caused by multiple factors.The main pathological features of AD are senile plaques(SP)which composed of amyloid (3 peptide(Aβ),tau protein abnormal accumulation of neurofibrillary tangle formation(NFT) and the loss of neurons and synapses. Nowadays,due to the complexity of the pathogenesis of AD.Clinical drug only can ameliorate the condition of AD patients, the occurrence of the disease can not be reversed. With the development of the pathogenesis of AD, many attempts to develop drugs treating it,but there is still no effective treatment available. Traditional Chinese medicine(TCM) which is characterized with multiple targets and multi-channel,TCM showing its unique advantages in the treatment of many complicated diseases. Therefore, we consider that compared with a single target for the treatment of chemical drugs,TCM maybe a more effective way to alleviate the condition of AD by the unique characteristics.Liuweidihuang(LW) is the classical formula for enriching yin and nourishing kidney.we have confirmed that the active fractions of LW are polysaccharides, oligosaccharides and glycosides by tracking with the effective components in LW, and we formulated the new type-5 of Traditional Chinese medicine which named Liuweidihuang glucoside(LW-AFC).It composed of three active fractions. Base on the physiological of the diease which treated by LW are working on nerve, endocrine, immunoregulation, we deduce that keep the balance of NIM is the working hypothesis of LW-AFC. Previous studies found that, LW-AFC can improve the object recognition memory, spatial learning and memory, both active and passive avoidance response capability of sporadic AD animal models SAMP8 (senescence accelerated mouse prone-8) and the familial AD animal models APP/PS1 double transgenic mice, suggesting that LW-AFC can prevent AD, but its specific targets and mechanism was not clear.In this study, in order to reveal the specific targets and mechanisms of LW-AFC preventing AD, based on the immunoregulation function, through behavior evaluation, synaptic plasticity detected by LTP, investgate the cytokine in peripheral blood and detected the lymphocyte subpopulations, explore the possible mechanism of LW-AFC prevent AD. Furthermore, by inflammatory cell mode, tested the immunomodulatory in peripheral immune system and central nervous system with LW-AFC active fraction and portion of the compounds from LW-AFC; Based on the current clinical drug targets of AD treatment:AChE, BACE1 and Aβ aggregation, the pharmacological activity of active compounds of LW-AFC was evalued. We can get the following main conclusions:1. Synaptic plasticity is the biological basis of learning and memory function,LW-AFC can significantly improve synaptic plasticity of mice with inflammation.2. LW-AFC regulate the balance of lymphocyte subsets of mice with inflammation.3. LW-AFC can significantly reduce proinflammatory cytokine TNFα, IL-6, IL-12, INFγ in peripheral blood and regulate the secretion of IL-10.4. LW-AFC active fraction:D-b, B-B, CA30 can regular the secretion of TNFα in CNS and peripheral immune cells.5. LW-AFC active compound:verbascoside, isoverbascoside, gallic acid can inhibit the Aβ aggregation, the IC50 of the three is 7.898×10-5M,3.206×10-5M,5.884×10-5M respectively.6. Pachymic acid has a weak inhibition activity on AChE, IC50=4.501×10-3 M. |
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