Saponins Effect on Human Insulin Amyloid Aggregation
The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric specie...
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MDPI AG
2024-12-01
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| author | Eleonora Mari Silvia Vilasi Paolo Moretti Maria Rosalia Mangione Giorgia Giorgini Roberta Galeazzi Maria Grazia Ortore |
| author_facet | Eleonora Mari Silvia Vilasi Paolo Moretti Maria Rosalia Mangione Giorgia Giorgini Roberta Galeazzi Maria Grazia Ortore |
| author_sort | Eleonora Mari |
| collection | DOAJ |
| description | The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular environment. Many efforts have been and are devoted to the search for cosolvents and cosolutes able to interfere with amyloid aggregation. In this work, we intensively study the effect of saponins, bioactive compounds, on human insulin aggregation. To monitor the kinetic of amyloid aggregation following secondary structure changes, we perform fluorescence and UV-Visible absorption spectroscopies, using Thioflavin T and Congo Red as amyloid specific probes, and Circular Dichroism. To study the overall structural features and size of aggregates, we perform Synchrotron Small-Angle X-ray Scattering and Dynamic Light Scattering experiments. The morphology of the aggregates was assessed by Atomic Force Microscopy. To deepen the understanding of the saponins interaction with insulin, a Molecular Dynamics investigation is performed, too. The reported data demonstrate that saponins interfere with the amyloid aggregation by inducing a strong inhibition on the formation of insulin fibrils, likely through specific interactions with insulin monomers. A dose-dependent effect is evident, and amyloid inhibition is already clear when saponins are just 0.01% <i>w</i>/<i>w</i> in solution. We suggest that saponins, which are natural metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea stars and cucumbers, can be promising metabolites to inhibit human insulin aggregation. This basic research work can pave the way to further investigations concerning insulin amyloidosis, suggesting the use of saponins as amyloid inhibitors and/or stabilizing agents in solution. |
| format | Article |
| id | doaj-art-06200e66851a4f7aa2d6ce9a25d2e5a4 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-06200e66851a4f7aa2d6ce9a25d2e5a42025-01-24T13:24:57ZengMDPI AGBiomolecules2218-273X2024-12-011514010.3390/biom15010040Saponins Effect on Human Insulin Amyloid AggregationEleonora Mari0Silvia Vilasi1Paolo Moretti2Maria Rosalia Mangione3Giorgia Giorgini4Roberta Galeazzi5Maria Grazia Ortore6Department of Life and Environmental Sciences, Marche Polytechnic University, I-60131 Ancona, ItalyInstitute of Biophysics, CNR, I-90146 Palermo, ItalyDepartment of Life and Environmental Sciences, Marche Polytechnic University, I-60131 Ancona, ItalyInstitute of Biophysics, CNR, I-90146 Palermo, ItalyDepartment of Life and Environmental Sciences, Marche Polytechnic University, I-60131 Ancona, ItalyDepartment of Life and Environmental Sciences, Marche Polytechnic University, I-60131 Ancona, ItalyDepartment of Life and Environmental Sciences, Marche Polytechnic University, I-60131 Ancona, ItalyThe misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular environment. Many efforts have been and are devoted to the search for cosolvents and cosolutes able to interfere with amyloid aggregation. In this work, we intensively study the effect of saponins, bioactive compounds, on human insulin aggregation. To monitor the kinetic of amyloid aggregation following secondary structure changes, we perform fluorescence and UV-Visible absorption spectroscopies, using Thioflavin T and Congo Red as amyloid specific probes, and Circular Dichroism. To study the overall structural features and size of aggregates, we perform Synchrotron Small-Angle X-ray Scattering and Dynamic Light Scattering experiments. The morphology of the aggregates was assessed by Atomic Force Microscopy. To deepen the understanding of the saponins interaction with insulin, a Molecular Dynamics investigation is performed, too. The reported data demonstrate that saponins interfere with the amyloid aggregation by inducing a strong inhibition on the formation of insulin fibrils, likely through specific interactions with insulin monomers. A dose-dependent effect is evident, and amyloid inhibition is already clear when saponins are just 0.01% <i>w</i>/<i>w</i> in solution. We suggest that saponins, which are natural metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea stars and cucumbers, can be promising metabolites to inhibit human insulin aggregation. This basic research work can pave the way to further investigations concerning insulin amyloidosis, suggesting the use of saponins as amyloid inhibitors and/or stabilizing agents in solution.https://www.mdpi.com/2218-273X/15/1/40amyloidsproteinssaponinshuman insulinsmall-angle X-ray scatteringcircular dichroism |
| spellingShingle | Eleonora Mari Silvia Vilasi Paolo Moretti Maria Rosalia Mangione Giorgia Giorgini Roberta Galeazzi Maria Grazia Ortore Saponins Effect on Human Insulin Amyloid Aggregation Biomolecules amyloids proteins saponins human insulin small-angle X-ray scattering circular dichroism |
| title | Saponins Effect on Human Insulin Amyloid Aggregation |
| title_full | Saponins Effect on Human Insulin Amyloid Aggregation |
| title_fullStr | Saponins Effect on Human Insulin Amyloid Aggregation |
| title_full_unstemmed | Saponins Effect on Human Insulin Amyloid Aggregation |
| title_short | Saponins Effect on Human Insulin Amyloid Aggregation |
| title_sort | saponins effect on human insulin amyloid aggregation |
| topic | amyloids proteins saponins human insulin small-angle X-ray scattering circular dichroism |
| url | https://www.mdpi.com/2218-273X/15/1/40 |
| work_keys_str_mv | AT eleonoramari saponinseffectonhumaninsulinamyloidaggregation AT silviavilasi saponinseffectonhumaninsulinamyloidaggregation AT paolomoretti saponinseffectonhumaninsulinamyloidaggregation AT mariarosaliamangione saponinseffectonhumaninsulinamyloidaggregation AT giorgiagiorgini saponinseffectonhumaninsulinamyloidaggregation AT robertagaleazzi saponinseffectonhumaninsulinamyloidaggregation AT mariagraziaortore saponinseffectonhumaninsulinamyloidaggregation |