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Updated: Jan 17, 2026
Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Inhibition of Insulin Amyloid Fibrillation by the Putative Anticancer Alkaloid Chelerythrine: Spectroscopic, Imaging,
Shukdeb Sing1, Arindam Das1, Gouranga Jana1
1Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore 721102, India.
Abstract:
Type-2 diabetes (T2D) is a major issue in the public health sector due to its high incidence and lack of global therapeutic options. The self-assembly behavior of human insulin (INS) can lead to membrane damage and cell dysfunction, which is directly linked to T2D ailment. The development of a potential therapeutic that can prevent the formation of amyloid fibrils is a promising strategy for the treatment of T2D ailment. Herein, we have used a natural alkaloid, chelerythrine, and explored its antiamyloidogenic function against INS fibrillation. Thioflavin T fluorescence and Congo red absorbance analysis revealed that chelerythrine can significantly suppress the INS fibrillation process. Circular dichroism and FTIR studies demonstrated that chelerythrine markedly reduced the β-sheet content of the INS fibrillar samples, indicating that chelerythrine inhibited the fibrillogenesis process. Tyrosine fluorescence analysis, Nile red analysis, and 8-anilino-1-napthalenesulfonic acid analysis also revealed that chelerythrine arrested the INS fibrillation, and the hydrophobic interaction between INS and chelerythrine played a critical role in this inhibitory process. Apart from the hydrophobic interaction, polar interaction and some other interactions may also be responsible for the inhibitory action of chelerythrine, which was revealed from molecular docking results. AFM imaging analysis strongly supported that the quantity of fibrils in the presence of chelerythrine was markedly less. Furthermore, chelerythrine has the potential to defibrillate existing fibrillar assemblies. Our work clearly elaborated the inhibitory effect of chelerythrine on INS fibrillation.
Insights
Chelerythrine, a natural alkaloid, effectively inhibits human insulin (INS) fibrillation, a key process in Type-2 diabetes (T2D). This compound prevents amyloid fibril formation and can even break down existing fibrils, offering a potential therapeutic strategy for T2D.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Type-2 diabetes (T2D) poses a significant public health challenge with limited therapeutic options.
- The self-assembly of human insulin (INS) into amyloid fibrils contributes to T2D pathogenesis by causing membrane damage and cellular dysfunction.
- Preventing INS fibrillation is a promising therapeutic strategy for T2D.
Purpose of the Study:
- To investigate the antiamyloidogenic potential of the natural alkaloid chelerythrine against human insulin (INS) fibrillation.
- To elucidate the mechanisms by which chelerythrine inhibits INS fibrillogenesis.
Main Methods:
- Thioflavin T fluorescence and Congo red absorbance assays to monitor fibrillation.
- Circular dichroism (CD) and FTIR spectroscopy to analyze secondary structure changes.
- Tyrosine fluorescence, Nile red, and 8-anilino-1-napthalenesulfonic acid assays to assess fibrillation.
- Atomic Force Microscopy (AFM) to visualize fibril formation.
- Molecular docking to predict interaction modes.
Main Results:
- Chelerythrine significantly suppressed INS fibrillation and reduced beta-sheet content in fibrillar samples.
- Chelerythrine arrested INS fibrillation, with hydrophobic interactions playing a key role, alongside polar and other interactions.
- AFM imaging confirmed a marked reduction in fibril quantity in the presence of chelerythrine.
- Chelerythrine demonstrated the ability to defibrillate pre-existing INS fibrillar assemblies.
Conclusions:
- Chelerythrine exhibits potent antiamyloidogenic activity against human insulin fibrillation.
- The findings highlight chelerythrine as a potential therapeutic agent for Type-2 diabetes by inhibiting INS fibrillogenesis.
- Chelerythrine's ability to both inhibit formation and disrupt existing fibrils offers a dual therapeutic approach.
