The composition of a centrifuged product obtained from the fresh leaves and stems of Melissa officinalis and skin irritation in the reconstituted human epidermis (Episkin model) have been investigated in comparison to the EtOH-H(2)O (1:1) extract obtained by Soxhlet from the dried plant. Two new sulfated triterpenes (1 and 2) and two ionol derivatives have been isolated for the first time from Melissa officinalis together with caffeic and rosmarinic acids. The structures of compounds 1 and 2 were established by analysis of their spectroscopic data. Both the centrifuged material and its major constituents neither affected cell viability nor caused the release of pro-inflammatory mediators or the decrease of trans-epithelial electrical resistance (TEER) in the reconstituted human epidermis.