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Anti-amyloidogenic properties of some phenolic compounds.

Porzoor A, Alford B, Hügel HM, Grando D, Caine J, Macreadie I - Biomolecules (2015)

Bottom Line: After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001).There was a significant reduction in the green fluorescence intensity associated with 14 compounds.The position and not the number of hydroxyl groups on the aromatic ring was found to be the most important determinant for the anti-amyloidogenic properties.

View Article: PubMed Central - PubMed

Affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. afsaneh.porzoor@rmit.edu.au.

ABSTRACT
A family of 21 polyphenolic compounds consisting of those found naturally in danshen and their analogues were synthesized and subsequently screened for their anti-amyloidogenic activity against the amyloid beta peptide (Aβ42) of Alzheimer's disease. After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001). TEM and immunoblotting analysis also showed that selected compounds were capable of hindering fibril formation even after prolonged incubations. These compounds were also capable of rescuing the yeast cells from toxic changes induced by the chemically synthesized Aβ42. In a second assay, a Saccharomyces cerevisiae AHP1 deletant strain transformed with GFP fused to Aβ42 was treated with these compounds and analyzed by flow cytometry. There was a significant reduction in the green fluorescence intensity associated with 14 compounds. We interpret this result to mean that the compounds had an anti-amyloid-aggregation propensity in the yeast and GFP-Aβ42 was removed by proteolysis. The position and not the number of hydroxyl groups on the aromatic ring was found to be the most important determinant for the anti-amyloidogenic properties.

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Chemical structures of analyzed polyphenolic compounds. (a) Compounds that reduced ThT associated fluorescent similar to EGCG; (b) compounds that were not found to be potent inhibitors of amyloid aggregation.
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biomolecules-05-00505-f002: Chemical structures of analyzed polyphenolic compounds. (a) Compounds that reduced ThT associated fluorescent similar to EGCG; (b) compounds that were not found to be potent inhibitors of amyloid aggregation.

Mentions: After 24 h co-incubation of compounds with Aβ42, rosmarinic acid, similar to EGCG (p < 0.001), exerted the most potent inhibitory effect on peptide aggregate formation (Figure 1c). Other compounds that showed aggregation inhibition capacity were 2,5-DHBA (gentisic acid), 3,4-DHCA (caffeic acid), 3,4,5-THBA (gallic acid), and salvianolic acid B (p < 0.005). 3,4-DHBA also significantly reduced the aggregation propensity of Aβ42 compared with the control sample (p < 0.01). On the other hand, caffeic acid trimers BA_PG65 and BA_PG69, as well as compounds BA_PG83 (p < 0.01) and BA_PG17 (p < 0.05), significantly contributed to the increased ThT associated fluorescence after 24 h co-incubation with chemically synthesized Aβ42. Further, the results suggest that these compounds accelerated the aggregation and fibril formation capacity of the peptide compared with the control sample (Figure 2a). Five compounds lowered the fluorescent intensity, indicating their capability in slowing aggregation and fibril formation (ThT negative). These were rosmarinic acid, 2,5-DHBA, 3,4-DHCA, 3,4,5-THBA (gallic acid), and salvianolic acid B (p < 0.05) (Figure 1d). The kinetic effect of EGCG on Aβ42 fibrillogenesis inhibition was unlike that of the other compounds. EGCG interacts early with Aβ42 and dissociates oligomer formation in a sustainable manner.


Anti-amyloidogenic properties of some phenolic compounds.

Porzoor A, Alford B, Hügel HM, Grando D, Caine J, Macreadie I - Biomolecules (2015)

Chemical structures of analyzed polyphenolic compounds. (a) Compounds that reduced ThT associated fluorescent similar to EGCG; (b) compounds that were not found to be potent inhibitors of amyloid aggregation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496683&req=5

biomolecules-05-00505-f002: Chemical structures of analyzed polyphenolic compounds. (a) Compounds that reduced ThT associated fluorescent similar to EGCG; (b) compounds that were not found to be potent inhibitors of amyloid aggregation.
Mentions: After 24 h co-incubation of compounds with Aβ42, rosmarinic acid, similar to EGCG (p < 0.001), exerted the most potent inhibitory effect on peptide aggregate formation (Figure 1c). Other compounds that showed aggregation inhibition capacity were 2,5-DHBA (gentisic acid), 3,4-DHCA (caffeic acid), 3,4,5-THBA (gallic acid), and salvianolic acid B (p < 0.005). 3,4-DHBA also significantly reduced the aggregation propensity of Aβ42 compared with the control sample (p < 0.01). On the other hand, caffeic acid trimers BA_PG65 and BA_PG69, as well as compounds BA_PG83 (p < 0.01) and BA_PG17 (p < 0.05), significantly contributed to the increased ThT associated fluorescence after 24 h co-incubation with chemically synthesized Aβ42. Further, the results suggest that these compounds accelerated the aggregation and fibril formation capacity of the peptide compared with the control sample (Figure 2a). Five compounds lowered the fluorescent intensity, indicating their capability in slowing aggregation and fibril formation (ThT negative). These were rosmarinic acid, 2,5-DHBA, 3,4-DHCA, 3,4,5-THBA (gallic acid), and salvianolic acid B (p < 0.05) (Figure 1d). The kinetic effect of EGCG on Aβ42 fibrillogenesis inhibition was unlike that of the other compounds. EGCG interacts early with Aβ42 and dissociates oligomer formation in a sustainable manner.

Bottom Line: After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001).There was a significant reduction in the green fluorescence intensity associated with 14 compounds.The position and not the number of hydroxyl groups on the aromatic ring was found to be the most important determinant for the anti-amyloidogenic properties.

View Article: PubMed Central - PubMed

Affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. afsaneh.porzoor@rmit.edu.au.

ABSTRACT
A family of 21 polyphenolic compounds consisting of those found naturally in danshen and their analogues were synthesized and subsequently screened for their anti-amyloidogenic activity against the amyloid beta peptide (Aβ42) of Alzheimer's disease. After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001). TEM and immunoblotting analysis also showed that selected compounds were capable of hindering fibril formation even after prolonged incubations. These compounds were also capable of rescuing the yeast cells from toxic changes induced by the chemically synthesized Aβ42. In a second assay, a Saccharomyces cerevisiae AHP1 deletant strain transformed with GFP fused to Aβ42 was treated with these compounds and analyzed by flow cytometry. There was a significant reduction in the green fluorescence intensity associated with 14 compounds. We interpret this result to mean that the compounds had an anti-amyloid-aggregation propensity in the yeast and GFP-Aβ42 was removed by proteolysis. The position and not the number of hydroxyl groups on the aromatic ring was found to be the most important determinant for the anti-amyloidogenic properties.

Show MeSH
Related in: MedlinePlus