This study aimed to investigate the chemical composition of Coccoloba uvifera leaves and evaluate the antioxidant and antitumor effects of the total extract and its major metabolites. Four assays were used to determine the antioxidant activity, including radical scavenging abilities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), radical cation, and ferric-reducing power. Additionally, vincristine was used as a reference medication to examine the anticancer activity on Ehrlich aesthete carcinoma cells (EACC). Nine compounds were isolated from C. uvifera leaves aqueous methanol extract. Their structures were identified as gallic acid (1), methyl gallate (2), protocatechuic acid methyl ester (3), protocatechuic acid (4), quercetin 3-O-β-d-glucopyranoside (isoquercitrin, 5), kaempferol 3-O-β-D-neohespridoside (6), myricitrin 4″-O-gallate (7), myricetin 3-O-β-d-glucopyranoside (8), and myricetin 3-O-arabinopyranoside (9). The majority possess noticeable antioxidant and antitumor properties. However, compounds 1, 5, 4, 2, and 7 displayed a strong antioxidant potential in terms of DPPH radical scavenging activity, with values of 85.72 ± 0.30, 82.16 ± 0.20, 81.34 ± 0.20, 79.62 ± 0.29, and 79.34 ± 0.20%, respectively. Compounds 4, 1, 5, 7, and 2 revealed high reducing power activity, with respective values of 1.348 ± 0.043, 1.303 ± 0.011, 1.154 ± 0.020, 1.058 ± 0.032, and 1.056 ± 0.019. Compounds 4 and 1 showed the highest ABTS radical scavenging capabilities (91.90 ± 0.24 and 91.83 ± 0.74%) and ferric-reducing power ability (1979 ± 14.53 and 1965 ± 26.86 μmol Trolox/100 g, respectively). Compound 4 has the highest level of cytotoxicity, resulting in 78.710.21% dead cells.
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