Neuroprotective effect of Bis(Indolyl)phenylmethane in Alzheimer's disease rat model through inhibition of hen Lysozyme amyloid fibril-induced neurotoxicity

Amyloid aggregates are the hallmarks of several disorders, including Huntington's, Parkinson's and Alzheimer's diseases. Compounds that could inhibit amyloid fibril formation and/or reduce their associated neurotoxicity might have therapeutic values for treating the diseases. In this work, bis(Indolyl)phenylmethane (BIPM) has been demonstrated to reduce formation of amyloid fibril by hen egg-white lysozyme (HEWL), and also, the effect of aggregates formed in the presence of compound on spatial learning and memory of rats was assessed using Morris water maze. It was found that the compound dose-dependency inhibited amyloid fibrils formation with the optimum concentration of 50 mu m. Our studies have shown that the compound was capable to directly disrupt the oligomerization of HEWL, and the resulting aggregates were non-toxic. Twenty-four male Wistar rats were divided into four groups: control, scopolamine, HEWL and BIPM. Our results indicated that BIPM-treated rats found platform with less distance traveled (n = 6, p < 0.05) and in less time (n = 6, p < 0.01), compared with the lysozyme group. The compound also increased the percentage of time elapsed (n = 6, p < 0.05) and the distance swum (n = 6, p < 0.001) in the target quadrant in the probe test. The extent of histological injury in the hippocampus was determined by Nissl and Congo red staining. A significant (n = 6, p < 0.05) increase in intact neurons and decrease in amyloid plaques were observed in the hippocampal CA1 region of the BIPM group. Our findings imply that BIPM improved spatial learning and memory by inhibiting amyloid fibril-induced neurotoxicity. In addition, we recommend the use of model proteins as an effective tool to explore the Alzheimer's disease pathogenesis.