Flavonoids and Ellagitannins Characterization, Antioxidant and Cytotoxic Activities of Phyllanthus acuminatus Vahl

Abstract

The phenolic composition of leaves from <i>Phyllanthus acuminatus</i> L., a plant commonly used in Costa Rica as traditional medicine, was studied using UPLC-ESI-MS on an enriched phenolic extract. A total of 20 phenolic compounds were identified, comprising eight flavonoids (two flavanones-pinocembrin isomers and six derivatives from apigenin, chrysin, quercetin, and kaempferol); seven ellagitannins, two flavan-3-ols (prodelphinidin B dimer and (epi)gallocatechin); and three phenolic acids (ellagic acid, trimethylellagic acid, and ferulic acid). All of these compounds are reported for the first time in <i>P. acuminatus</i>, while previously reported in the genus <i>Phyllanthus</i>. Antioxidant evaluation was performed for <i>P. acuminatus</i> phenolic extract obtaining DPPH results with a remarkably low IC₅₀ value of 0.15 μg/mL. Also, cytotoxicity on gastric AGS and colon SW20 adenocarcinoma cell lines was evaluated, and highly promising results were obtained, with IC₅₀ values of 11.3 μg/mL and 10.5 μg/mL, respectively. Furthermore, selectivity index values obtained when comparing cytotoxicity on normal Vero cells was SI > 20 for both cancer cell lines, indicating a particularly high selectivity. Additionally, Justicidin B, a metabolite extensively studied for its antitumoral activity, was isolated from a non-polar extract of <i>P. acuminatus</i>, and comparatively evaluated for both bioactivities. The DPPH value obtained for Justicidin B was moderate (IC₅₀ = 14.28 μg/mL), while cytotoxicity values for both AGS (IC₅₀ = 19.5 μg/mL) and SW620 (IC₅₀ = 24.8 μg/mL) cell lines, as well as selectivity when compared with normal Vero cells (SI = 5.4 and 4.2 respectively), was good, but lower than <i>P. acuminatus</i> extract. These preliminary results suggest that <i>P. acuminatus</i> enriched phenolic extract containing flavonoids, ellagitannins, flavan-3-ols, and phenolic acids, reported for the first time in this plant, could be of interest for further cancer cytotoxicity studies to elucidate structure-bioactivity relationships, and the molecular mechanisms and pathways.