Fibrillation of α‐lactalbumin: Effect of crocin and safranal, two natural small molecules from Crocus sativus

Abstract

Formation of toxic amyloid structures is believed to be associated with various late-onset neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The fact that many proteins in addition to those that are associated with clinical conditions have the potential to form amyloid fibrils in vitro provides opportunities for studying the fundamentals of protein aggregation and amyloid formation in model systems. Accordingly, considerable interest and effort has been directed toward developing small molecules to inhibit the formation of fibrillar assemblies and their associated toxicities. In the present study, we investigated the inhibitory effect of crocin and safranal, two principal components of saffron, on fibrillation of apo-alpha-lactalbumin (a-alpha-LA), used as a model protein, under amyloidogenic conditions. In the absence of any ligand, formation of soluble oligomers became evident after 18 h of incubation, followed by subsequent appearance of mature fibrils. Upon incubation with crocin or safranal, while transition phase to monomeric beta structures was not significantly affected, formation of soluble oligomers and following fibrillar assemblies were inhibited. While both safranal and crocin had the ability to bind to hydrophobic patches provided in the intermediate structures, and thereby inhibit protein aggregation, crocin was found more effective, possibly due to its simultaneous hydrophobic and hydrophilic character. Cell viability assay indicated that crocin could diminish toxicity while safranal act in reverse order.

Response Surface Methodology for Optimizing the Bovine Serum Albumin Fibrillation

“…Absorbance increase at 540 nm is a proven indicator of the amyloid structure [2]. However, a general increase is also occurring in the whole spectrum [14]. As a concrete example, typical Congo red spectra (Fig.…”

“…Characterization of amyloid structures is done, among other means, by the use of various probes interacting with amyloid beta-sheets including thioflavin T [33] and Congo red [32] or, as previously mentioned, via direct observation of fibrils by electron microscopy [14]. In general, aggregation of proteins is, formed of misfolded and partially unfolded states in competition with the normal folding pathway as in the case of BSA [8,20,44,46].…”

Protein-Protein interactions leading to aggregation: Perspectives on mechanism, significance and control

“…These compounds were previously reported to be effective against growth of malignant cells [218], and beneficial in cases of learning impairement [219]. Both compounds were shown to inhibit fibrillation of this protein, with crocin inhibiting oligomer formation, and possibly acting as a beta-sheet breaker [220].…”

Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review

“…1; ISO 3632 2011) which has been cultivated in Iran, Greece, Morocco, India, Spain and Italy (Ebrahim-Habibi et al 2010;Pintado et al 2011;Modaghegh et al 2008). Although the source of saffron is obscure, it is apparently originated from Asia Minor and Iran (Ahmad et al 2011).…”