Effect of Tilia x 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 x 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), alpha-pinene and beta-pinene, which presented a selective antiproliferative action on tumor lymphocytes (EC50 on tumor cells: 3.8 +/- 0.2 mu g/mL; EC50 on normal cells: 205 +/- 1.8 mu g/mL). While all monoterpenes exhibited this activity, limonene proved to be the most active (EC50 on tumor cells: 35 2.0 mu g/mL; EC50 on normal cells: 72 +/- 5.0 mu g/mL) also exerting a stimulatory effect on non-mitogen stimulated lymphocytes proliferation (% of stimulation respect to control) (mean +/- SEM): L 10 mu g/mL: 25 +/- 1.0%; 20 mu g/mL: 38.5 +/- 2.5%; L 40 mu g/mL: 41 +/- 0.9%; L 60 mu g/mL: 58.5 +/- 3%. T. x viridis may thus constitute a potential source of monoterpenes with immunomodulatory activity. Copyright (C) 2008 John Wiley & Sons, Ltd.