Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L

Abstract The PUNICA GRANATUM L. (pomegranate) by-product POMx was partitioned between water, EtOAc and N-BuOH, and the EtOAc and N-BuOH extracts were purified by XAD-16 and Sephadex LH-20 column chromatography to afford ellagic acid (1), gallagic acid (2), punicalins (3), and punicalagins (4). Compounds 1 - 4 and the mixture of tannin fractions (XAD-16 eluates) were evaluated for antioxidant, antiplasmodial, and antimicrobial activities in cell-based assays. The mixture of tannins (TPT), XAD-EtOAc, XAD-H 2 O, XAD-PJ and XAD-BuOH, exhibited IC 50 values against reactive oxygen species (ROS) generation at 0.8 - 19 μg/mL. Compounds 1 - 4 showed IC 50 values of 1.1, 3.2, 2.3 and 1.4 μM, respectively, against ROS generation and no toxicity up to 31.25 μg/mL against HL-60 cells. Gallagic acid (2) and punicalagins (4) exhibited antiplasmodial activity against PLASMODIUM FALCIPARUM D6 and W2 clones with IC 50 values of 10.9, 10.6, 7.5 and 8.8 μM, respectively. Fractions XAD-EtOAc, XAD-BuOH, XAD-H 2 O and XAD-PJ compounds 1 - 4 revealed antimicrobial activity when assayed against ESCHERICHIA COLI, PSEUDOMONAS AERUGINOSA, CANDIDA ALBICANS, CRYPTOCOCCUS NEOFORMANS, methicillin-resistant STAPHYLOCOCCUS AUREUS (MRSA), ASPERGILLUS FUMIGATUS and MYCOBACTERIUM INTRACELLULARE. Compounds 2 and 4 showed activity against P. AERUGINOSA, C. NEOFORMANS, and MRSA. This is the first report on the antioxidant, antiplasmodial and antimicrobial activities of POMx isolates, including structure-activity relationships (SAR) of the free radical inhibition activity of compounds 1 - 4. Our results suggest a beneficial effect from the daily intake of POMx and pomegranate juice (PJ) as dietary supplements to augment the human immune system’s antioxidant, antimalarial and antimicrobial capacities.