Metabolite Profiling of Antioxidant Rich Fractions of Punica granatum L. Mesocarp and CD36 Expression Regulation

Abstract

Objective It was aimed at determining which polyphenolic compound(s) in pomegranate mesocarp extract (PME) is liable for the antioxidant, anti-glycation and anti-CD36 activities. Methods The PME was fractionated using liquid-liquid extraction method. The fractions were tested for their polyphenolic content, antioxidant potency, anti-glycation activity and anti-CD36 potential. The metabolite compositions of PME and derived fractions were investigated in an untargeted manner using metabolomics in relation to its antioxidant and anti-glycation activities. Results The ethyl acetate and n-butanol fractions of the pomegranate mesocarp demonstrated highest antioxidant and anti-glycation potencies. These fractions, represented by gallic and ellagic acids monomers, were enriched in tannins and phenolic acids. Orthogonal partial least squares discriminate analysis (OPLS-DA) modeling of ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolite profiles from the different pomegranate mesocarp fractions indicated that gallic and ellagic acids were potential contributors to the antioxidant and anti-glycation effects of the pomegranate mesocarp. At cellular level, the polyphenolic-rich crude extract as well as the ethyl acetate, n-butanol and aqueous residual fractions suppressed the protein expression of CD36. The anti-CD36 activity of these extracts and fractions was attributed to the presence of punicalagin, the ellagitannins that occurred in equal amount in the different fractions. Conclusion This work demonstrated the protective effect of the non-edible part of the pomegranate fruit and showed that gallic and ellagic acids account for the antioxidant and anti-glycation activities while punicalagin is liable for the anti-CD36 activity of PME.