Methyl gallate – Rich fraction of Syzygium coriaceum leaf extract induced cancer cell cytotoxicity via oxidative stress
Rummun N., Pires E., McCullagh J., Claridge TWD., Bahorun T., Li WW., Neergheen VS.
© 2020 SAAB Whilst the pharmacological potential of Syzygium species is well reported in the literature, data on the Mauritian endemic Syzygium species is limited. Thus, the in vitro antioxidant and anti-proliferative properties of three endangered Syzygium species, endemic to Mauritius, were investigated. Leaves samples of the three species were exhaustively extracted with a hydro-methanolic solvent and the antioxidant activities of the derived extracts were evaluated using a battery of six in vitro models. The antiproliferative effect of S. coriaceum was evaluated against lung carcinoma (A549), liposarcoma (SW872) and hepatocellular carcinoma (HepG2) cell lines. Further, the effect of S. coriaceum on intracellular reactive oxygen species (ROS) generation, intrinsic antioxidant enzymes activities and DNA damage in HepG2 cells were studied. MTT guided-fractionation coupled with mass spectrometry, column chromatography and NMR spectroscopy analysis was employed to characterise the bioactive entities in S.coriaceum. S.coriaceum showed the most potent antioxidant activities in all six assay models and also induced a dose-dependent decrease in the cell viability. S. coriaceum treatment in HepG2 cells resulted in a dose-dependent increase in the level of ROS with a 4.4 fold increment at 100 µg/mL (p ≤ 0.0001). The surge in ROS level was corroborated by a parallel dose-dependent decrease in antioxidant enzyme activities. A significant 80.5% drop in glutathione peroxidase activity was observed at 40 µg/mL (p ≤ 0.0001). Spectroscopic analysis revealed gallic acid (1) and methyl gallate (2) as major bioactive components in S. coriaceum leaf extract along with quercitrin (3), quercetin 3-O-β-D-xylopyranosyl-(1→2)-α-L-rhamnopyranoside (4), tellimagrandin I (5), and 3,4,6-tri-O-galloyl-D-glucose (6). Analysis of HepG2 cells treated with commercially available gallic acid and methyl gallate showed a similar trend in activities as S. coriaceum leaf extract. Collectively, these results demonstrated that S. coriaceum and its major bioactive phenolics: gallic acid and methyl gallate, may effectively induce cell death in HepG2 cells via upregulation of ROS.