Oligomeric procyanidins inhibit insulin fibrillation by forming unstructured and off-pathway aggregates

Shaohuang Chen1, Huiting Yin1, Lei Zhang1

  • 1State Key Laboratory of Chemical Engineering, Tianjin Key Laboratory of Membrane Science and Desalination Technology, School of Chemical Engineering and Technology, Tianjin University Tianjin 300072 China surx@tju.edu.cn.

RSC Advances
|May 2, 2022
PubMed

Insights

Oligomeric procyanidins (OPCs) and resveratrol effectively inhibit insulin amyloid fibrillation by promoting off-pathway aggregation. This suggests polyphenolic structures are key for preventing degenerative disease-linked protein aggregation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Amyloid fibril accumulation is linked to human degenerative diseases.
  • Natural polyphenols show potential in preventing these diseases by inhibiting amyloid formation.
  • The precise molecular mechanisms of polyphenol anti-amyloidogenesis remain unclear.

Purpose of the Study:

  • To investigate the anti-amyloidogenic effects of oligomeric procyanidins (OPCs), resveratrol, and trehalose on insulin.
  • To elucidate the molecular mechanisms underlying polyphenol-mediated inhibition of amyloid formation.

Main Methods:

  • Thioflavin-T (ThT) fluorescence assays
  • Dynamic Light Scattering (DLS)
  • Circular Dichroism (CD) spectroscopy
  • Transmission Electron Microscopy (TEM)

Main Results:

  • The inhibitory efficacy against insulin amyloid fibrillation followed the order: OPCs > resveratrol > trehalose.
  • OPCs demonstrated potent inhibition across all fibrillation stages, redirecting aggregation to unstructured, off-pathway aggregates.
  • Polyphenolic structure is crucial for effective inhibition of fibril deposition.

Conclusions:

  • OPCs and resveratrol exhibit significant anti-amyloidogenic properties by interfering with the insulin aggregation pathway.
  • Naturally occurring polyphenols, particularly OPCs, offer a promising avenue for developing therapeutic strategies against amyloid-related diseases.

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