{"title":"Raw <i>Inonotus obliquus</i> polysaccharide counteracts Alzheimer's disease in a transgenic mouse model by activating the ubiquitin-proteosome system.","authors":"Shumin Wang, Kaiye Dong, Ji Zhang, Chaochao Chen, Hongyan Shuai, Xin Yu","doi":"10.4162/nrp.2023.17.6.1128","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong><i>Inonotus obliquus</i> has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer's disease (AD), which is widely considered to be type III diabetes. To investigate whether <i>I. obliquus</i> can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw <i>Inonotus obliquus</i> polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice).</p><p><strong>Materials/methods: </strong>SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting.</p><p><strong>Results: </strong>Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%.</p><p><strong>Conclusions: </strong>Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.</p>","PeriodicalId":19232,"journal":{"name":"Nutrition Research and Practice","volume":"17 6","pages":"1128-1142"},"PeriodicalIF":2.0000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694425/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition Research and Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4162/nrp.2023.17.6.1128","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/20 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background/objectives: Inonotus obliquus has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer's disease (AD), which is widely considered to be type III diabetes. To investigate whether I. obliquus can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw Inonotus obliquus polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice).
Materials/methods: SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting.
Results: Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%.
Conclusions: Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.
期刊介绍:
Nutrition Research and Practice (NRP) is an official journal, jointly published by the Korean Nutrition Society and the Korean Society of Community Nutrition since 2007. The journal had been published quarterly at the initial stage and has been published bimonthly since 2010.
NRP aims to stimulate research and practice across diverse areas of human nutrition. The Journal publishes peer-reviewed original manuscripts on nutrition biochemistry and metabolism, community nutrition, nutrition and disease management, nutritional epidemiology, nutrition education, foodservice management in the following categories: Original Research Articles, Notes, Communications, and Reviews. Reviews will be received by the invitation of the editors only. Statements made and opinions expressed in the manuscripts published in this Journal represent the views of authors and do not necessarily reflect the opinion of the Societies.