Urtica dioica L. leaf chemical composition: A never-ending disclosure by means of HR-MS/MS techniques

[Display omitted] •A nettle leaf alcoholic extract was profiled by UHPLC-HRMS/MS techniques.•Dereplication tool tentatively disclosed heretofore unidentified compounds.•Hydroxycinnamic acid derivatives were the most representative constituents.•Low cytotoxicity up to 12.5 μg/mL was observed on ARPE-19 and Caco-2 cell lines. The metabolite profiling of plant extracts always represents an exciting challenge, as the chemical diversity of natural products is still far beyond the researchers’ imagination, even focusing on a plant that is thought to have already been broadly investigated. Herein UHPLC-HRMS/MS techniques were applied to an alcoholic crude extract from nettle leaves and proved to be a precious tool for the disclosure of secondary metabolites never found before. Hydroxycinnamic acid derivatives were the most representative constituents, with a 2-caffeoilisocitric acid cyclodimer described for the first time, besides four C-glycosylated flavones, bearing a 3-hydroxy-3-methylglutaryl function. This deep investigation paves the way for the isolation and full characterization of these molecules by means of spectroscopic techniques. Moreover, based on preliminary cytotoxicity evaluation, further research on the use of this nettle extract as a valuable nutraceutical product is encouraged.