Tu-Xian Decoction ameliorates diabetic cognitive impairment by inhibiting DAPK-1  

作　　者：WANG Danyang YAN Bin WANG An SUN Qing PANG Junyi CUI Yangming TIAN Guoqing 

机构地区：[1]Department of Traditional Chinese Medicine,Peking Union Medical College Hospital,Beijing 100730,China [2]Chinese Academy of Mediucal Sciences&Peking Union Medical College,Beijing 100730,China [3]Department of Pathology,Peking Union Medical College Hospital,State Key Laboratory of Complex Severe and Rare Disease,Molecular Pathology Research Center,Beijing 100730,China [4]Animal Research Laboratory Platform,Peking Union Medical College Hospital,the National Science and Technology Key Infrastructure on Translational Medicine,Beijing 100730,China

出　　处：《Chinese Journal of Natural Medicines》2023年第12期950-960,共11页中国天然药物（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.82074404).

摘　　要：Tu-Xian decoction(TXD),a traditional Chinese medicine(TCM)formula,has been frequently administered to manage diabetic cognitive impairment(DCI).Despite its widespread use,the mechanisms underlying TXD’s protective effects on DCI have yet to be fully elucidated.As a significant regulator in neurodegenerative conditions,death-associated protein kinase-1(DAPK-1)serves as a focus for understanding the action of TXD.This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1.To this end,a diabetic model was established using Sprague-Dawley(SD)rats through a high-fat,high-sugar(HFHS)diet regimen,followed by streptozotocin(STZ)injection.The experimental cohort was stratified into six groups:Control,Diabetic,TC-DAPK6,high-dose TXD,medium-dose TXD,and low-dose TXD groups.Following a 12-week treatment period,various assessments—including blood glucose levels,body weight measurements,Morris water maze(MWM)testing for cognitive function,brain magnetic resonance imaging(MRI),and histological analyses using hematoxylin-eosin(H&E),and Nissl staining—were conducted.Protein expression in the hippocampus was quantified through Western blotting analysis.The results revealed that TXD significantly improved spatial learning and memory abilities,and preserved hippocampal structure in diabetic rats.Importantly,TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region.These results underscore TXD's potential in mitigating DCI via DAPK-1 inhibition,positioning it as a viable therapeutic candidate for addressing this condition.Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.

关 键 词：Tu-Xian decoction Traditional Chinese medicine Diabetes complications Diabetic cognitive impairment Death associated protein kinase-1 

分 类 号：R965[医药卫生—药理学]