Inhibition of Amyloid Fibrillation of Insulin by Bisdemethoxycurcumin

Amyloid fibrillation of proteins or protein misfolding followed by the deposition and accumulation of amyloid fibrils in organs and tissues causes some serious amyloid-related diseases, such as neurodegenerative disorders (Alzheimer s, Parkinson s, Huntington s diseases), type II diabetes and more than 20 other human diseases. This is a major problem for therapeutic proteins such as insulin. Since its discovery in 1921, insulin has been isolated and produced in commercial quantities to treat insulin-dependent diabetics. A major problem confronting the industry is insulin aggregation during processing and delivery of the protein-drug. The therapeutic strategies for the treatment of amyloidogenic disorders have been proposed in two pathways, which are the inhibition of amyloid formation and disruption of the formed amyloid assemblies. Natural polyphenolic compounds, which are found extensively in foods and herbal remedies, have been demonstrated to disrupt amyloid structures and to attenuate the cytotoxicity of amyloid fibrils. Numerous reports have suggested that the anti-oxidant property and the Specific structure of polyphenols are involved in their anti-amyloid activity. Curcumin is an active principle of the perennial herb Curcuma longa Linn, generically known as turmeric. The active component of turmeric (curcumin, demethoxycurcumin, and bisdemethoxycurcumin), are commonly known as curcuminoids, has caught attention as a potential treatment for diabetes and its complications primarily. In the present study, the inhibitory activities of bisdemethoxycurcumin (BDMC) on the amyloid fibrillation of human insulin (HI) as an appropriate model protein for in vitro fibrillation was investigated using thioflavin T (ThT) fluorescence. Also, the binding interaction evaluations were carried out using fluorescence quenching. Results showed that amyloid fibrillation of HI was inhibited effectively by BDMC. The inhibitory activity of BDMC can be used in drug formulation against the dangerous amyloid-related diseases and provide health promotion for organs and tissues of the body.