Bin Li , Jiaxin Li , Yanwei Hao , Peijun Xie , Shengnan Yue , Shaofeng Wang , Jing Zhang , Yi Zhang
{"title":"Yuanzhi Powder inhibits tau pathology in SAMP8 mice: Mechanism research of a traditional Chinese formula against Alzheimer's disease","authors":"Bin Li , Jiaxin Li , Yanwei Hao , Peijun Xie , Shengnan Yue , Shaofeng Wang , Jing Zhang , Yi Zhang","doi":"10.1016/j.jep.2023.116393","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><p>Yuanzhi Powder (YZP), a classical Chinese medicine formula, is good at tonifying heart-Qi and improving cognitive ability. YZP has been reported to show therapeutic effect on alleviating the symptoms of Alzheimer's disease (AD).</p><p><em>Aim of the study</em>: This study was conducted to observe the effects of YZP on improving the cognitive abilities of SAMP8 mice, and explore the involved mechanisms on inhibiting the excessive accumulation of phosphorylated tau.</p></div><div><h3>Material and methods</h3><p>Thirty SAMP8 mice were randomly divided into five groups: AD group, AD + DO group, AD + YZP group, AD + LAC group and AD + LAC + YZP group. Age-matched SAMR1 mice were served as CTL group. AD + LAC group and AD + LAC + YZP group received 1 μg Lactacystin solution via intra-cerebroventricular injection. All mice (except the CTL group and AD + LAC group) were intragastrically administrated for 8 consecutive weeks. Then, the Morris Water Maze (MWM) test was conducted for evaluation of learning and memory abilities. The pathological changes of hippocampal CA1 were observed by Hematoxylin & eosin (H&E) staining. The expression of 26S proteasome in the hippocampus was measured by Western Blot (WB) and immunohistochemistry (IHC). The expressions of total tau (Tau5) and hyperphosphorylated <em>tau</em> (pS199, pT231 and pS396) were detected by WB. The aggregation of hyperphosphorylated <em>tau</em> and the binding ability of tau protein to microtubules were evaluated respectively by immunostaining and Thioflavin-S staining <em>and double</em>-label <em>immunofluorescence.</em></p></div><div><h3>Results</h3><p>SAMP8 mice showed serious cognitive impairment in behavioral tests. However, treatment of YZP significantly ameliorated the cognitive deficits of SAMP8 mice. The H&E staining suggested that YZP could protect against neuronal loss in SAMP8 mice. The IHC and WB results showed that YZP increases 26S proteasome expression in SAMP8 mice and 26S proteasome <em>expression</em> was <em>effectively</em> inhibited by Lactacystin. Meanwhile, The WB results demonstrated that YZP can inhibit the expression of hyperphosphorylated tau (pT231, pS396 and pS199). Furthermore, the immunostaining and Thioflavin-S staining <em>and double</em>-label <em>immunofluorescence</em> results indicated that YZP attenuates the excessive aggregation of hyperphosphorylated <em>tau and</em> enhances the binding ability of <em>tau</em> to stabilize microtubules in SAMP8 mice.</p></div><div><h3>Conclusions</h3><p>YZP could enhance cognitive performance and learning of AD, ameliorate tau pathology and significantly improve the binding ability of tau to microtubules, based potentially on inhibiting the excessive aggregation of hyperphosphorylated tau via the <em>26S</em>proteasome pathway but not necessarily the only one.</p></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874123002611","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 1
Abstract
Ethnopharmacological relevance
Yuanzhi Powder (YZP), a classical Chinese medicine formula, is good at tonifying heart-Qi and improving cognitive ability. YZP has been reported to show therapeutic effect on alleviating the symptoms of Alzheimer's disease (AD).
Aim of the study: This study was conducted to observe the effects of YZP on improving the cognitive abilities of SAMP8 mice, and explore the involved mechanisms on inhibiting the excessive accumulation of phosphorylated tau.
Material and methods
Thirty SAMP8 mice were randomly divided into five groups: AD group, AD + DO group, AD + YZP group, AD + LAC group and AD + LAC + YZP group. Age-matched SAMR1 mice were served as CTL group. AD + LAC group and AD + LAC + YZP group received 1 μg Lactacystin solution via intra-cerebroventricular injection. All mice (except the CTL group and AD + LAC group) were intragastrically administrated for 8 consecutive weeks. Then, the Morris Water Maze (MWM) test was conducted for evaluation of learning and memory abilities. The pathological changes of hippocampal CA1 were observed by Hematoxylin & eosin (H&E) staining. The expression of 26S proteasome in the hippocampus was measured by Western Blot (WB) and immunohistochemistry (IHC). The expressions of total tau (Tau5) and hyperphosphorylated tau (pS199, pT231 and pS396) were detected by WB. The aggregation of hyperphosphorylated tau and the binding ability of tau protein to microtubules were evaluated respectively by immunostaining and Thioflavin-S staining and double-label immunofluorescence.
Results
SAMP8 mice showed serious cognitive impairment in behavioral tests. However, treatment of YZP significantly ameliorated the cognitive deficits of SAMP8 mice. The H&E staining suggested that YZP could protect against neuronal loss in SAMP8 mice. The IHC and WB results showed that YZP increases 26S proteasome expression in SAMP8 mice and 26S proteasome expression was effectively inhibited by Lactacystin. Meanwhile, The WB results demonstrated that YZP can inhibit the expression of hyperphosphorylated tau (pT231, pS396 and pS199). Furthermore, the immunostaining and Thioflavin-S staining and double-label immunofluorescence results indicated that YZP attenuates the excessive aggregation of hyperphosphorylated tau and enhances the binding ability of tau to stabilize microtubules in SAMP8 mice.
Conclusions
YZP could enhance cognitive performance and learning of AD, ameliorate tau pathology and significantly improve the binding ability of tau to microtubules, based potentially on inhibiting the excessive aggregation of hyperphosphorylated tau via the 26Sproteasome pathway but not necessarily the only one.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.