Effects Of Bushen Yizhi Formula And It’s Extract On Senescence Accelerated Mouse

BackgroundAlzheimer’s disease is one of the most common progressive neuro-degenerative diseases,the prevalence is gradually increased with age that even reaches 50%morbidity at the age of 85.It places an enormous burden on social and medical system.The etiology of Alzheimer disease is not yet fully illustrated and the pathogenesis is complex.At present,there still no available western medicine that can stop or reverse the progression of this disease.Traditional Chinese medicine treatment of AD attracts more and more attention.Bushen Yizhi Formula(BSYZF),a Chinese prescription(consist of Fructus cnidii,Chinese wolfberry,Glossy privet fruit,Ginseng,Prepared fleece flower root and Cortex moutan)that have been proved by our department,to be capable of ameliorating the symptoms of Alzheimer’ s Disease(AD)in patients and animal models.Moreover,the drug-containing serum has certain protective effect on AD cells model.BSYZ-E is the effective ethyl acetate extract components of Bushenyizhi formula,which had been proved by our department that can ameliorate cellular injury in glutamate-induced PC12 cell,promote cell proliferation,down-regulate Aβ 1-42,reduce APP and PS1.We now show that BSYZF and BSYZ-E can improve behavioral performance in the senescence-accelerated prone 8(SAMP8)mice model of AD.In addition,BSYZ-E can also reduce inflammatory response in SAMP8.Our study suggested that BSYZF and BSYZ-E might be potential drug for AD.ObjectiveTo study the efficacy of BSYZF and BSYZ-E on ameliorating the AD pathology and learning memory ability in 6-month old SAMP8 mice following 4 weeks of treatment.Futher more,to dectetive whether BSYZ-E can ameliorate the pathology of AD by reducing inflammation reaction.MethodsThe 6-month-old male SAMP8 were randomly divided into 6 groups:SAMP8 model group,low-dose BSYZF group,middle-dose BSYZF group,high-dose BSYZF group,low-dose BSYZ-E group,high-dose BSYZ-E group;In addition,male Senescence-accelerated-resistant(SAMR1)with the same age as the negative controlgroup.A daily dose of BSYZF(1.46 g/kg.day,2.92 g/kg.day,5.84 g/kg.day),BSYZ-E(5.84g/kg · day,23.36g/kg.day)and Donepezil(3mg/kg.day)were given orally to SAMP8 mice and normal saline(NS)to SAMR1 mice and control-fed SAMP8 mice which were used as the control and model once a day for 28 days.Spatial learning and memory were tested by Morris water maze test and passive avoidance test.Levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)in the brain tissue was quantified by ELISA.The expression ofperoxisome proliferator-activated receptor-γ(PPAR-γ)and cyclooxygenase-2(COX-2)were measured by immunohistochemistry;protein levels of PPAR-γ,tumor necrosis factor-α(TNF-α),P65-nuclear factor-kappaB(P65-NF-κ B),phospho-p65NF-κ B and inducible nitric oxide synthase(iNOS)were measured by western Blotting.ResultsA daily dose of BSYZ-E given for 28 days significantly decreased levels of cortex phospho-p65NF-κ B,COX-2,iNOS as well as pro-inflammatory cytokines(TNFα,IL-1 β and IL-6)in SAMP8 mice brain versus controls,accompanied by increased PPAR-γ concentrations.Our results showed that Learning and memory ability which were detected by Morris water maze test and passive avoidance test also can be improved in Donepezil、BSYZF and BSYZ-E treated groups.ConclusionOur studies on Western blot,Immunohistochemical and ELISA measurements demonstrated that PPAR-γ level was increased whereas TNF-α,NF-κ B,phospho-p65NF-κB,COX-2,iNOS,IL-1β and IL-6 levels were decreased in BSYZ-E-fed SAMP8 mice compared to control-fed mice.In summary,the BSYZ-E treatment could increase PPAR-γ,decrease phospho-p65NF-κ B,COX-2,iNOS and pro-inflammatory factors(such as TNF-α,IL-1 β and IL-6).More importantly,BSYZF and BSYZ-E treatment could also improve cognitive performance of SAMP8 mice during Morris water maze test and passive avoidance test.Our results first demonstrated that BSYZ-E have neuroprotective effects on ameliorating inflammations that may give rise to AD in SAMP8 mice,which may be the mechanism for its effect on improving learning and memory ability.Taken together,these results suggested that BSYZF and BSYZ-E should be explored further as potential drug for AD.