The Effect of Polyphenols on Cellular and Isolated Proteasomes

Abstract

This study investigated the impact of phenyl-γ-valerolactones (PVLs), key metabolites of flavan-3-ols, on isolated and cellular proteasomes, employing both APPwt and APPmut cellular models of AD. The results demonstrate that PVLs have an inhibitory effect on proteasomes, with the mutated amyloid precursor protein gene (APPmut) cells being more susceptible to this treatment. The interaction between polyphenols and proteasomes presents a promising avenue for understanding cellular health dynamics. This study aimed to investigate the effect of polyphenols on both cellular and isolated proteasomes. The primary objective was to discern the impact of polyphenol exposure on proteasome activity and its potential implications for cellular functions. In vitro studies were conducted using a range of polyphenolic compounds, including flavonoids and phenolic acids. Cellular models were employed to assess the influence of polyphenols on cellular proteasome activity, while isolated proteasomes were subjected to polyphenol treatments to discern direct interactions. The findings revealed significant modulatory effects of polyphenols on both cellular and isolated proteasomes and C2 had strong inhibitory effects on constitutive proteasome activity, with IC50 values ranging from 0.01619 μM to 0.08738 μM. Additional compounds, PGPH and BrAAP, also had inhibitory effects on both proteasome subtypes. Flavonoids demonstrated a dose-dependent enhancement of proteasome activity in cellular models, while phenolic acids exhibited varying effects. Isolated proteasomes responded differently to specific polyphenols, suggesting compound-specific interactions. This study provides novel insights into the intricate relationship between polyphenols and proteasomes, highlighting their potential impact on cellular health. Understanding these interactions could pave the way for targeted interventions in diseases associated with proteasome dysfunction, offering new perspectives on the potential therapeutic roles of polyphenols.