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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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Cytotoxicity effect of freshly prepared HFIP pretreated Aβ42 peptide (5 μM) on C. glabrata cells.
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biomolecules-05-00505-f004: Cytotoxicity effect of freshly prepared HFIP pretreated Aβ42 peptide (5 μM) on C. glabrata cells.

Mentions: The cytotoxicity effect of 5 μM hexafluoroisopropanol (HFIP) pretreated Aβ42 [56] and the protection of the five selected phenolic compounds (50 μM) were tested on C. glabrata cells. The survival rate of yeast cells in the presence of Aβ42 was only ~10% of the untreated control sample (Figure 4). All of the selected phenolic compounds were capable of inhibiting toxicity to the C. glabrata cells when compared with the control. Salvianolic acid B (p < 0.001), gentisic acid, gallic acid, and caffeic acid (p < 0.005) were the most effective (Figure 3).


Anti-amyloidogenic properties of some phenolic compounds.

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

Cytotoxicity effect of freshly prepared HFIP pretreated Aβ42 peptide (5 μM) on C. glabrata cells.
© Copyright Policy
Related In: Results  -  Collection

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

biomolecules-05-00505-f004: Cytotoxicity effect of freshly prepared HFIP pretreated Aβ42 peptide (5 μM) on C. glabrata cells.
Mentions: The cytotoxicity effect of 5 μM hexafluoroisopropanol (HFIP) pretreated Aβ42 [56] and the protection of the five selected phenolic compounds (50 μM) were tested on C. glabrata cells. The survival rate of yeast cells in the presence of Aβ42 was only ~10% of the untreated control sample (Figure 4). All of the selected phenolic compounds were capable of inhibiting toxicity to the C. glabrata cells when compared with the control. Salvianolic acid B (p < 0.001), gentisic acid, gallic acid, and caffeic acid (p < 0.005) were the most effective (Figure 3).

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