Dendrobium huoshanense stem polysaccharide protects against Alzheimer's disease by modulating SCFAs/GLP-1 axis-mediated neuroinflammation suppression

  • Int J Biol Macromol. 2026 Apr:353:151235. doi: 10.1016/j.ijbiomac.2026.151235.
Qiang-Ming Li  1 ,  Qiao-Qiao Zhang-Yang  1 ,  Ya-Yi Tan  2 ,  Xiang-Ling Wu  2 ,  Xue-Qiang Zha  1 ,  Zhen-Zi Shang  3 ,  Jian-Ping Luo  4 ,  Feng-Yun Zhang  5
Affiliations
  • 1. School of Food and Biological Engineering, Anhui Province Institute of Agricultural Products Processing Technology, Engineering Research Center of Bio-Process of Ministry of Education, Hefei University of Technology, Hefei, 230009, People's Republic of China.
  • 2. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People's Republic of China.
  • 3. School of Food and Biological Engineering, Anhui Province Institute of Agricultural Products Processing Technology, Engineering Research Center of Bio-Process of Ministry of Education, Hefei University of Technology, Hefei, 230009, People's Republic of China; School of Biological and Environmental Engineering, Chaohu University, Hefei, 238024, People's Republic of China.
  • 4. School of Food and Biological Engineering, Anhui Province Institute of Agricultural Products Processing Technology, Engineering Research Center of Bio-Process of Ministry of Education, Hefei University of Technology, Hefei, 230009, People's Republic of China. Electronic address: [email protected].
  • 5. School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People's Republic of China. Electronic address: [email protected].
PMID: 41794249 DOI: 10.1016/j.ijbiomac.2026.151235
Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. The stem of Dendrobium huoshanense is a traditional medicinal food. This study aimed to investigate the effect of cultivated D. huoshanense stem polysaccharide (cDHPS) on AD and elucidate its mechanisms using an Aβ1-42-induced AD mouse model. Results showed that cDHPS significantly improved the cognitive dysfunction and ameliorated the hippocampal neuronal injury of AD mice. Meanwhile, cDHPS effectively alleviated the neuroinflammation of AD mice not only by decreasing the expression of Caspase-1, NOD-like Receptor family pyrin domain-containing 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC), as well as their downstream inflammatory cytokines, but also by inhibiting the activation of microglia and astrocytes. Furthermore, the levels of glucagon-like peptide-1 (GLP-1) in the hippocampus, plasma, and intestine of AD mice were markedly elevated by cDHPS, along with an increase in intestinal short-chain fatty acids (SCFAs) levels. However, the treatment of exendin 9-39, a GLP-1 Receptor antagonist, weakened the protective effect of cDHPS against AD, and the depletion of SCFAs reversed the beneficial effects of cDHPS on cognitive dysfunction, hippocampal neuronal injury, neuroinflammation, and GLP-1 secretion in AD mice. These results suggest that cDHPS could protect against AD by modulating the SCFAs/GLP-1 axis-mediated neuroinflammation suppression.

Keywords
Alzheimer's disease; Cultivated Dendrobium huoshanense stem polysaccharide; GLP-1; Neuroinflammation; SCFAs.
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