Mechanism of the protective effect of 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside on MPTP-induced Parkinson's disease mice

Histol Histopathol. 2026 Mar;41(3):479-492. doi: 10.14670/HH-18-968. Epub 2025 Jul 16.

Abstract

Background and purpose: Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of Polygonum multiflorum Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process.

Methods: The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing.

Results: TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflammation and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent.

Conclusion: TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Gastrointestinal Microbiome / drug effects
  • Glucosides* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents* / pharmacology
  • Stilbenes* / pharmacology

Substances

  • Glucosides
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • Stilbenes
  • Neuroprotective Agents
  • 2',3',4',5'-tetrahydroxystilbene-2-O-beta-D-glucoside