An investigation on amyloid beta plaque dissociation in differentiated SH-SY5Y cells of in vitro digested pomegranate peel polyphenols

In this study, the biological activities on Alzheimer's disease of pomegranate peel (Punica granatum L.) after in-vitro digestion were evaluated. The peel was subjected to in-vitro gastrointestinal digestion, and the polyphenol profiles before and after digestion were analyzed by high-performance liquid chromatography with diode array detection (HPLC-DAD). Human glioblastoma cells (U87MG) were used to model Aβ1-42-induced toxicity and plaque formation, and the effects of digested (DPP) and non-digested peel (PP) were investigated on cytotoxicity, Aβ aggregation, and fibril morphology. In addition, lipopolysaccharide (LPS)-induced inflammation in Raw264.7 macrophages was evaluated by quantifying the expression of inflammation-related genes (iNOS, IL-6, TNF-α, NF-κB, COX-2, and IL-10) using qRT-PCR. The results showed that polyphenols partially degraded during digestion but retained measurable bioactivity. Both PP and DPP, at non-toxic concentrations, supported cell viability, reduced Aβ1-42 aggregation, and modulated the expression of pro- and anti-inflammatory genes. These findings suggest that pomegranate peel, even after digestion, preserves certain anti-amyloidogenic and immunomodulatory activities. Although the study is limited to in-vitro digestion and cell culture models, the findings indicate that pomegranate peel could serve as a sustainable bioactive component for functional foods or dietary supplements.