Insulin Sensitivity of Adipocytes is Improved by Pomegranate Mesocarp Through Reduced Oxidative Stress and Inflammation.

OBJECTIVE: Inflammatory phenomena and increase in oxidative stress in cell physiopathology progression render therapeutic strategies based on nutritional antioxidants necessary. It was thus aimed at assessing the effectiveness of the pomegranate mesocarp extract (PME) on differentiation of preadipocytes to adipocytes in the presence/absence of hydrogen peroxide (H2O2), a model mimicking insulin resistance. METHOD: The effect of PME on lipid accumulation, protein expression of antioxidant, inflammatory and adipogenic biomarkers, reactive oxygen species production, activity of antioxidant enzymes and secretion of IL-6 has been evaluated during the differentiation of preadipocytes to adipocytes, in the presence or absence of H2O2. RESULTS: H2O2 reduced the expression of the regulator of insulin sensitivity PPARγ and suppressed adipocyte differentiation. PME counteracted the effect of H2O2. The latter induced a higher level of fat accumulation by promoting the expressions of the adipogenic markers PPARγ, C/EBPα, FABP4 and CD36 as compared to the control and the H2O2-treated differentiating cells. During the progression of adipogenesis, highest increase (p < 0.05) in IL-6 secretion, by 3.16 and 3.85 folds, was observed on day 2 of differentiation in control and H2O2-treated cells, respectively, compared to day 0. PME significantly decreased (p < 0.01) the secretion of the cytokine in addition to suppressing the expression of NFκB. PME also prevented the reduction of superoxide dismutase, catalase and glutathione peroxidase activities that occurred during adipogenesis, by at most 33%, 119% and 42%, respectively. CONCLUSION: These findings indicate that PME efficiently improves insulin sensitivity and can significantly counteract oxidative stress and inflammation.

Anti-Neurodegenerating Activity: Structure-Activity Relationship Analysis of Flavonoids.

An anti-neurodegeneration activity study was carried out for 80 flavonoid compounds. The structure-activity analysis of the structures was carried out by performing three different anti-neurodegeneration screening tests, showing that in these structures, the presence of a hydroxy substituent group at position C3' as well as C5' of ring B and a methoxy substituent group at the C7 position of ring A play a vital role in neuroprotective and antioxidant as well as anti-inflammatory activity. Further, we found structure (5) was the top-performing active structure out of 80 structures. Subsequently, a molecular docking study was carried out for the 3 lead flavonoid compounds (4), (5), and (23) and 21 similar hypothetical proposed structures to estimate the binding strength between the tested compounds and proteins potentially involved in disease causation. Ligand-based pharmacophores were generated to guide future drug design studies.

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

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.