CYTOTOXIC POTENTIAL OF VALERIAN CONSTITUENTS AND VALERIAN TINCTURES

Underground parts of three Valeriana species, namely V. officinalis L. s.l., V. wallichii DC. (V. jatamansi Jones), and V. edulis Nutt. ex T orr & Gray ssp. procera (H.B.K.) F. G. Meyer (V. mexicana DC.), are us ed in phytotherapy because of their mild sedative properties. Characte ristic constituents of these species, which are regarded also as the a ctive principles, were tested for cytotoxicity against GLC(4), a human small-cell lung cancer cell line, and against COLO 320, a human color ectal cancer cell line, using the microculture tetrazolium (MTT) assay . Valepotriates of the diene type (valtrate, isovaltrate and acevaltra te) displayed the highest cytotoxicity, with IC50 values of 1-6 mu M, following continuous incubation. The monoene type valepotriates (didro valtrate and isovaleroxyhydroxydidrovaltrate) were 2- to 3-fold less t oxic. Baldrinal and homobaldrinal, decomposition products of valepotri ates, were 10- to 30-fold less toxic than their parent compounds. Isov altral had a higher cytotoxicity than its parent compound isovaltrate. Valerenic acids (valerenic acid, acetoxyvalerenic acid, hydroxyvalere nic acid and methyl valerenate), which are characteristic for V. offic inalis, had a low toxicity with IC50 values between 100 and 200 mu M. Freshly prepared and stored tinctures, prepared from roots and rhizome s of the three valerian species, were analysed for valepotriates, bald rinals and valerenic acids, and also tested for cytotoxicity. There wa s a clear relationship between the valepotriate contents of the freshl y prepared tinctures and their toxicity. Upon storage, valepotriates d ecomposed, which was reflected in a significant reduction of the cytot oxic effect.