Alzheimer’s Disease Prevention through Natural Compounds: Cell-Free<i>, In Vitro</i>, and <i>In Vivo</i> Dissection of Hop (<i>Humulus lupulus</i> L.) Multitarget Activity
Alessandro Palmioli, Valeria Mazzoni, Ada De Luigi, Chiara Bruzzone, Gessica Sala, Laura Colombo, Chiara Bazzini, C Zoia, Mariagiovanna Inserra, Mario Salmona, Ivano De Noni, Carlo Ferrarese, Luisa Diomede, Cristina Airoldi
Abstract
The relevant social and economic costs associated with aging and neurodegenerative diseases, particularly Alzheimer's disease (AD), entail considerable efforts to develop effective preventive and therapeutic strategies. The search for natural compounds, whose intake through diet can help prevent the main biochemical mechanisms responsible for AD onset, led us to screen hops, one of the main ingredients of beer. To explore the chemical variability of hops, we characterized four hop varieties, i.e., Cascade, Saaz, Tettnang, and Summit. We investigated the potential multitarget hop activity, in particular its ability to hinder A1-42 peptide aggregation and cytotoxicity, its antioxidant properties, and its ability to enhance autophagy, promoting the clearance of misfolded and aggregated proteins in a human neuroblastoma SH-SY5Y cell line. Moreover, we provided evidence of in vivo hop efficacy using the transgenic CL2006Caenorhabditis elegans strain expressing the A3-42 peptide. By combining cell-free and in vitro assays with nuclear magnetic resonance (NMR) and MS-based metabolomics, NMR molecular recognition studies, and atomic force microscopy, we identified feruloyl and p-coumaroylquinic acids flavan-3-ol glycosides and procyanidins as the main anti-A components of hop.