Hepatocellular carcinoma (HCC) is the most fatal cancer globally with limited treatment options. Plants and herbs have been used to treat cancer and other diseases for a long time by traditional practitioners in Sri Lanka. In the present study, leaf and bark extracts of selected plants were investigated for cytotoxic properties on HepG2 cells. Anti-oxidant activity and total phenolic and flavonoid contents were also determined. Plant extracts that exerted cytotoxic effects on the HepG2 cell line with IC50 <100 μg/mL were tested on normal liver epithelial cells (THLE-3). Out of the 56 extracts, 21 exhibited potent cytotoxic effects (IC50 < 100 µg/mL) on HepG2 cells after 48 h exposure, and 12 were less toxic (IC50 > 100 μg/mL) to THLE-3 normal liver cells. Six extracts exhibited potent radical scavenging activity with EC50 < 100 μg/mL against 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, while 17 extracts showed potent anti-oxidant activity (Trolox equivalents > 100 mg/g) against ferric reducing anti-oxidant power (FRAP) assay. Out of the 56 extracts, 15 had total phenolic content above 100 mg/g of gallic acid equivalents, and 4 had flavonoid content above 100 mg/g of quercetin equivalents. Among the extracts screened, hexane, dichloromethane, ethyl acetate, and methanol extracts of Allophylus cobbe leaves (IC50 – 9.388, 6.8, 19.95, and 11.3 μg/mL, respectively), Madhuca longiflora bark (IC50 – 14.42 μg/mL), methanol extract of Munronia pinnata bark (IC50 – 52.06 μg/mL), and hexane, dichloromethane, ethyl acetate, and methanol extracts of Adenanthera bicolor (IC50 – 45.86, 27.35, 24.56, and 61.83 μg/mL, respectively) exerted potent cytotoxicity against HepG2 with less toxicity (IC50 > 100 μg/mL) to THLE-3 cells after 48 h of incubation. These findings provide a direction to isolate possible anti-cancer compounds for hepatocellular carcinoma.
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