An investigation on amyloid beta plaque dissociation in U87MG cells of in-vitro digested pomegranate peel

This study evaluated the bioactivity of pomegranate peel, particularly after simulated gastrointestinal digestion, in an in-vitro Alzheimer's disease model. Human glioblastoma U87MG cells exposed to Aβ_1-42 were used to assess the effects of both digested and non-digested pomegranate peel on Aβ aggregation and inflammatory responses. In-vitro digestion simulated oral, gastric, and intestinal phases, and polyphenol profiles were analyzed before and after digestion. Cytotoxicity was examined using MTT assays, Aβ disaggregation by ELISA, and fibril morphology by field emission scanning electron microscopy (FESEM). Anti-inflammatory activity was evaluated via qRT-PCR in LPS-stimulated Raw264.7 macrophages, focusing on iNOS, IL-6, TNF-α, NF-κB, COX-2, and IL-10 expression. Despite partial degradation during digestion, both forms of peel retained bioactivity. At non-toxic concentrations, they supported cell viability and reduced Aβ aggregation (57.21% for non-digested, 42.11% for digested peel). FESEM confirmed fibril disruption, and both forms downregulated pro-inflammatory genes while enhancing IL-10 expression. These findings suggest that pomegranate peel, even after digestion, preserves anti-amyloidogenic and immunomodulatory activities in-vitro, supporting its potential as a dietary ingredient that merits further investigation in the context of Alzheimer's disease.