Effect of Tilia × viridis flower extract on the proliferation of a lymphoma cell line and on normal murine lymphocytes: contribution of monoterpenes, especially limonene

Tilia species are widely used in Europe as medicinal plants. The selective antiproliferative activity of a Tilia cordata flower dichloromethane extract (DME) on a lymphoma cell line has been reported previously and in order to extend this to other unstudied Tilia species, the effect of Tilia × viridis DME on the proliferation of tumor and normal murine lymphocytes was investigated. The bioguided fractionation of DME yielded a fraction rich in limonene (L), α ‐pinene and β ‐pinene, which presented a selective antiproliferative action on tumor lymphocytes (EC 50 on tumor cells: 3.8 ± 0.2 µg/mL; EC 50 on normal cells: 205 ± 1.8 µg/mL). While all monoterpenes exhibited this activity, limonene proved to be the most active (EC 50 on tumor cells: 35 ± 2.0 µg/mL; EC 50 on normal cells: 72 ± 5.0 µg/mL) also exerting a stimulatory effect on non‐mitogen stimulated lymphocytes proliferation (% of stimulation respect to control) (mean ± SEM): L 10 µg/mL: 25 ± 1.0%; 20 µg/mL: 38.5 ± 2.5%; L 40 µg/mL: 41 ± 0.9%; L 60 µg/mL: 58.5 ± 3%. T. × viridis may thus constitute a potential source of monoterpenes with immunomodulatory activity. Copyright © 2008 John Wiley & Sons, Ltd.