Several natural products have been proven to prevent neurodegenerative disorders by potentiating the action of nerve growth factor (NGF). Among them, secoiridoids have recently attracted interest for their potential use as neuritogenic compounds. A source of these compounds is the root of Gentiana lutea L. used in food products to improve digestion. The aim of this work was to evaluate the neuritogenic activity of methanolic extracts of cultivated, wild and commercial roots of G. lutea using rat pheochromocytoma (PC12) cells. Neuritogenic activity was assessed by xCELLigence real time cell analysis system (RTCA DP), neurite outgrowth image analysis and immunofluorescence staining. Extracts at 12.5 and 25 mu g/ml with or without NGF showed a marked stimulation of neuritogenesis, without cytotoxic effects, and their neuritogenic action was synergistic to NGF activity. These results represent the first evidence of the neuritogenic effects of G. lutea and of its potential use as a functional food ingredient. (C) 2015 Elsevier Ltd. All rights reserved.