Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Raw Inonotus obliquus polysaccharide counteracts Alzheimer's disease in a transgenic mouse model by activating the ubiquitin-proteosome system

  • Shumin Wang (School of Basic Medicine, Dali University) ;
  • Kaiye Dong (Department of Ophthalmology, The First Affiliated Hospital of Dali University) ;
  • Ji Zhang (College of Clinical Medicine, Dali University) ;
  • Chaochao Chen (College of Clinical Medicine, Dali University) ;
  • Hongyan Shuai (School of Basic Medicine, Dali University) ;
  • Xin Yu (School of Basic Medicine, Dali University)
  • Received : 2023.06.05
  • Accepted : 2023.09.14
  • Published : 2023.12.01
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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.

Keywords

Acknowledgement

We thank Dr. Su Yingzhen, Kunming University, for helpful discussions on topics related to this work and Dr.Gong Zhiting, School of Basic Medical Science, Dali University, for providing the 3× Tg-AD mice model.

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