The Therapeutic Effects Of Dianxianning Tablet On Alzheimer's Disease Model In Caenorhabditis Elegans And Its Pharmacological Mechanisms

Recent researches have shown that antiepileptic drugs levetiracetam,lamotrigine and topiramate suppress cognitive impairment of learning and memory in the AD mouse model,suggesting that they are effective on AD.However,severe toxicity may limit their further application.Traditional Chinese medicine(TCM)are usually characterized of multi-component and multi-target in the treatment of serious and complex chronic diseases,but there are many gaps from TCM for treating epilepsy on their further application in AD.Transgenic Caenorhabditis elegans expressing human A? were used as a pathological model to screen for therapeutic agents to ameliorate A? toxicity among various TCM for treating epilepsy.The results showed that DXP,GS and DXN could significantly reduced A?-induced toxicities in C.elegans,and the effect of DXN is much better than DXP and GS,so we chose DXN for further study.Furthermore,the mechanisms of DXN against A? toxicity were studied in this paper,the results showed that DXN strongly ameliorated A? toxicity in the C.elegans might be a consequence of the shift from the toxic A? oligomer to less-toxic A? monomer.Besides,DXN significantly suppressed the expression of hsp-16.2 induced by juglone in the strain TJ375 and dropped to 55.2%.DXN also up-regulated sod-3 expression to 182% in CF1553.These results indicated that DXN protected C.elegans against oxidative stress.Futhermore,DXN significantly activate DAF-16 in C.elegans,but not SKN-1.RNAi assay also showed that suppression of the A? toxicity by DXN was significantly inhibited by daf-16 RNAi,but not by hsf-1 RNAi and skn-1 RNAi.These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN.Morris water maze test was employed to assess the effect of DXN on learning and memory ability of mice,the results showed that DXN significantly decreased escape latency of dysmnesia mice induced by scopolamine in the hidden platform trial,at the same time increased time,distance and number of platform-site crossovers in the target quadrant in the probe trial.These results indicated that DXN markedly improved the ability of learning and memory of dysmnesia mice induced by scopolamine.All the results support that DXN is a potential drug candidate to battle against Alzheimer's diseases.