Investigating immune-modulating polysaccharides as potential therapies for Alzheimer’s disease (AD)

  • Fang Cheng

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Alzheimer’s disease (AD) is a leading cause of dementia with limited treatment options. Plant-derived immunomodulating polysaccharides are being investigated for potential therapeutic benefits. This study focused on a pure arabinan isolated from Sida cordifolia root, building on previous findings of its crude polysaccharide’s immunomodulatory properties in APP/PS1 mice. This Sida cordifolia arabinan (referred to as SCA) was structurally characterized by GLC-MS and NMR spectroscopy. In vitro studies showed SCA significantly enhanced immune activity in RAW 264.7 and SIM-A9 cells, increasing cytokines production. SCA was identified as a broad-spectrum immunomodulator with mechanisms similar to fucoidan, particularly in regulating IL-8 production and gene expression through the TLR4/MD-2 complex and activating NF-κB and JNK signalling pathways. In vivo studies confirmed SCA’s safety and demonstrated its ability to enhance cytokine responses and improve gut microbiome health, which may influence AD pathology via the gut-brain axis. Additionally, screening of other plant sources found that only hemp polysaccharides activated immune cells, which needs further studies in future. This thesis highlights an arabinan from Sida cordifolia as a promising immunomodulator with potential therapeutic applications for AD, particularly through enhancing immune responses and regulating gut microbiota. Further studies, including complete clarification of the mechanisms of action of SCA in more cell models and animal models and investigation of the long-term effects of SCA both in vitro and in vivo, are needed in the future before conducting the clinical trials.

Thesis is embargoed until 31st December 2029.

Date of AwardDec 2024
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsChina Scholarship Council
SupervisorBrian Green (Supervisor), Gary Hardiman (Supervisor) & Xiaobei Pan (Supervisor)

Keywords

  • polysaccharide
  • bioactivity
  • immunomodulation
  • plant sources
  • gut microbiota

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