Phyto-beta-SERM formulation for menopause and Alzheimer's disease: From bench to bedside

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a traditional Chinese medicinal herb, has been used for thousands of years as a tonic and anti-aging agent, and frequently used to treat dementia in China. 2,3,5,4’-tetrahydroxy stilbene-2-O-s-D-glucoside (TSG) is one of the active components extracted from Polygonum multiflorum, showing obviously neuroprotection effects in several AD-like models, but the exact mechanism is still not understood. To investigate the pharmacological mechanisms of TSG on AD therapy, we observed the lesion of MAPKs signal transduction pathway in the brain of different age AD-like transgenic animal and cellular models and to explore the protective effect of the drug. Methods: APP695V717I transgenic (Tg) mice were observed from 4 to 16 month old. The Tg mice were randomly divided into model group (4 month, 10 month and 16 month old), and TSG group at dose of 0.05,0.1 and 0.2g/kg/d. Control adopted the same age and background C57BL/6J mice. The animals were administered intragastrically by the drug or water from 4 to 10 month old. For untreated 10 month APP Tg mice, TSG low dose and middle dose were administrated to them from 10 to 16 month old. APP695 wild-type transfected SH-SY5Y neuroblastoma cell (SH-SY5Y APP695) was incubated with TSG at dose of 1,10 and 100mg/ml for 24 hours. Control adopted the untransfected SH-SY5Y neuroblastoma cells. The mRNA expression was measured by gene chips (80s mice full sequence gene chips, more than 8,000 genes). The protein expression was detected by western-blotting methods. Results: Several components (PKC, ERK, p70S6K) in Mitogen activated protein kinases (MAPKs) signal transduction pathway were abnormally expressed and activated both in APP Tg mice and SH-SY5Y APP695 cells. The changes of MAPKs were related with the different age of APP transgenic mice. TSG improved the MAPKs signal transduction pathway and maintain the survival and normal function of neural cells at the AD-like animal and cellular models. Conclusions: TSG not only prevents the occurrence of abnormal lesion of MAPKs signal transduction pathway in early stage of AD-like model but also reverse the abnormal lesion in late stage of AD-like model. TSG indicate effectiveness in neural protection on several targets relating to AD, so it would be benefit for the treatment of AD and other neurodegenerative diseases. Our research finds a possible therapeutic application to neurodegenerative disease, as well as provides new strategies for prevention and treatment of AD.