Inhibition of the formation of amyloid-like fibrils using herbal extracts

Abstract

We tested the amyloid fibril formation inhibitory effect of seven teas diluted in 55% ethanol at pH 7.0 at a protein concentration of 0.15 mg/ml α-chymotrypsin. In the experiments we investigated the formation and inhibition of amyloid fibrils by turbidity measurements, aggregation kinetics experiments and Congo red binding assay. The results suggest that the different teas effectively inhibit the formation of amyloidlike fibrils. The two most potent inhibitors were peppermint and melilot, extracts which almost completely inhibited the formation of aggregates in 5-fold dilution. The inhibitory effect on the aggregation formation of melilot and peppermint extracts was concentration dependant. The extent of inhibition was found to be proportional with the total concentration of phenolic compounds.

Cyanine dyes derived inhibition of insulin fibrillization

“…As seen in Figures 2A,B, 3A, insulin samples treated with cyanine dyes at low dye-protein ratio 0.5, showed 2-28 times lower ThT fluorescence intensity (coupled with much smaller turbidity) than a control sample (not containing the cyanine dye), that displayed the largest ThT fluorescence response and the highest turbidity [55,56]. Accordingly, the kinetic parameters of the protein fibrillization significantly differ from those of the control sample, reflecting the inhibition of the protein aggregation (Table 1).…”

“…The coincubation of trimethine/pentamethine/heptamethine compounds with the insulin samples resulted in a rise of both lag time, up to 7.5 times (suppressed nucleation) and k , up to 3.2 times (enhanced elongation) compared to the control values, with the exception of AK3-5, AK5-3, AK5-9, which retarded the elongation and slowed down the nucleation of insulin fibrils. Notably, the experimental conditions affecting the nucleation and elongation do not always induce the changes of kinetic parameters in the same direction [56,57]. Taking into account the facts that the insulin secondary structure changes from almost completely helical to predominant β-sheets [58], and that the hydrophobic core of insulin (B-chain, the residues 11-17 [40]) is exposed to solvent during partial unfolding of the protein (enhanced by NaCl), followed by the formation of oligomers and protofibrils [45,57], it can be…”

“…: i) the increase in length of the aliphatic substituents on the nitrogen atom of benzazole chromophore from 1 to 2 and more carbons enhances the inhibition potency (decreased max 0 / FF ) of trimethines (AK3-3, AK3-5, AK3-7 compared to AK3-1) and pentamethines (AK5-3, AK5-4, AK5-9 compared to AK5-1, AK5-2). Interestingly, pentamethine dyes, possessing long alkyl chains in the quaternized nitrogen were reported to have far more higher affinity for bovine serum albumin than those with short substituents on the nitrogen atom of benzazole chromophore, suggesting that the novel dyes could inhibit amyloid fibril formation by interaction with native proteins [56]; ii) the presence of benzyl substituent in the N-alkyl substituents of benzazole moiety reduces the ability of AK3-11, AK5-6, AK7-6 to inhibit the insulin amyloid formation; iii) the replacement of S by Se in the benzazole heterocycle had negative impact on the inhibitory potential of AK5-2 and AK5-4 compared to AK5-1 and AK5-3, respectively; iv) the presence of CN  group in the N-alkyl of AK5-8 and the alkyl substituents in the 5-th and 6-th positions of benzazole moiety of AK3-8 decreases the dye inhibition potency; v) the long alkyl substituents of the quinoline ring, containing Nmethylpyrrolidine and N-methylpiperidine groups significantly reduce the ability of the monomethines to interfere with the insulin aggregation; vi) the OH-groups of the aliphatic substituents on the nitrogen atom of the benzazole chromophore (AK3-7 and AK5-9) induce 2-4…”

APLICACIÓN DE LAS ANTOCIANINAS OBTENIDAS A PARTIR DE Zea mays L. (MAÍZ MORADO) COMO AGENTES INHIBIDORES DE LA AGREGACIÓN DE LOS PÉPTIDOS AMILOIDE Y TIPO AMILOIDE (TRIPSINA AGREGADA)

“…Las diluciones se realizaron a partir de una solución de 55 % etanol / 10 mM buffer fosfato. Cuanto más concentrados eran los extractos, presentan una mayor reducción en la turbidimetría (casi completa en el caso del meliloto) 20 . En nuestro trabajo, obtuvimos una disminución máxima de la turbidimetría de las fibrillas del 66.61 % para una concentración de 230.77 μg/mL de antocianinas (concentración más alta en este estudio).…”

Avocado Juice Prevents the Formation of Trypsin Amyloid-Like Fibrils in Aqueous Ethanol

“…19 A number of studies have shown that polyphenolic compounds inhibit the fibril formation. [20][21][22][23][24] The antihypertensive, lipid-lowering, antiobesity, antidiabetic, antiatherosclerotic, antithrombotic, and cardioprotective effects of avocado have been demonstrated in many studies. 16 The avocado fruit phytochemicals also can provide a beneficial nutrition strategy for cancer prevention.…”