Antioxidant activities in a cell-free system correlated well with the result obtained from the cell-based assay, revealing that the hydroethanolic extract of PN could concentration-dependently ameliorate hydrogen peroxide-induced stress in human endothelial cells more effectively than the water extract, without affecting DNA damage. The highest cytotoxicity was observed with both extracts of TC, which was also the ingredient of PN that showed the most potent antioxidant activity. Toxicity of TC might arise from its major constituent gallic acid, which can act as either an antioxidant or a pro-oxidant, depending on its concentration and cell types tested. Gallic acid was previously reported to exert its cytotoxicity through the generation of H2O2 in testicular cells.33 Furthermore, the hydroethanolic extract of PN became cytotoxic at 10-fold higher concentrations, resulting in a safety factor of approximately 10. Meanwhile, the water extract of PN showed a narrow margin of safety, with a safety factor of approximately 2. The considerably less cytotoxic effect of PN suggested that the extraction of the combined herbs with 50% ethanol could convey the synergistic antioxidant activities of the polyherbal formula while reducing the overall toxicity, supporting the traditional wisdom in the use of polyherbal formula.