Cytotoxic activity of Moroccan Melissa officinalis leaf extracts and HPLC-ESI-MS analysis of its phytoconstituents

Melissa officinalis L. is a medicinal and aromatic plant traditionally used in Morocco to treat a weave range of illness. The aim of our study was to evaluate cytotoxic activity of Moroccan Melissa officinalis leaf extracts against three human cancer cell lines, namely, MCF7, LNCAP and PC3 and to reevaluate its phytochemicals. The dichloromethane extract was found to be the most active cytotoxic extract, decreasing cell viability in a dose-dependent manner, especially against the breast MCF7 cell line. The IC50 values for the dichloromethane extract against MCF7, LNCAP, and PC3 cell lines were 30.90, 71.21, and 173.93 μg/mL respectively whereas the corresponding IC50 values for the ethanol extract were 35.52, 136.40, and 237.82 μg/mL. An update of the chemical profiles of these organic extracts was conducted by GC-MS, HPLC, and HPLC-ESI-MS, and the quantity of total polyphenolic compounds (on a dry weight basis) was 61.84 g/kg and 2.86 g/kg in the ethanol and dichloromethane extracts, respectively. The major polyphenolic compounds identified in the ethanol extract were 3,4-dihydroxyphenyl lactic acid (I), 3,4-dihydroxybenzoic acid (II), caffeic acid (III), luteolin-7-O-glucoside (IV), rosmarinic acid glucoside (V), methyl caffeate (VI), rosmarinic acid (VII), isolithospermic acid (VIII), methyl rosmarinate (IX), lithospermic acid (X), methyl isolithospermic acid (XI), and methyl lithospermic acid (XII). Of these, 3,4-dihydroxyphenyl lactic acid (I), isolithospermic acid along with its methyl ester derivative are reported in Melissa officinalis leaves extract for the first time. In addition, o-tyrosol (XIII), methyl hydroxyphenyl acetic acid (XIV), and cis-rosmarinic acid (XV) were also detected in the DCM extracts. In the n-hexane extracts LCFA (palmitic, linolenic, linoleic, and stearic acids), sterols (campesterol, β-sitosterol, and stigmasterol), and the vitamins (α- and β-tocopherol) were detected and identified. These results indicated that Melissa officinalis L extracts possess a potent cytotoxic effect against human cancer cell lines and the richness of this herb in bioactive molecules justifying its use in traditional Moroccan pharmacopeia.