NF-κB MODULATORS FROM VALERIANA OFFICINALIS 917 Copyright © 2006 John Wiley & Sons, Ltd. Phytother. Res. 20, 917–919 (2006) DOI: 10.1002/ptr Copyright © 2006 John Wiley & Sons, Ltd. PHYTOTHERAPY RESEARCH Phytother. Res. 20, 917–919 (2006) Published online 14 August 2006 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ptr.1972 SHORT COMMUNICATION NF- κ κ κ B Modulators from Valeriana officinalis Nadia J. Jacobo-Herrera 1 †, Nina Vartiainen 2 , Paul Bremner 1 ‡, Simon Gibbons 1 , Jari Koistinaho 2,3 and Michael Heinrich 1 * 1 Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, UK 2 Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland 3 Department of Oncology, Kuopio University Hospital, Kuopio, Finland Valeriana officinalis (Valerianaceae) has been of great interest for its therapeutic uses for treating mild nervous tension and temporary sleeping problems. In traditional European medicine it has been also reported as an antiinflammatory remedy. This study reports that the EtOAc extract of the underground parts of V. officinalis showed inhibitory activity against NF- κ κ κB at 100 μg/mL in the IL-6/Luc assay on HeLa cells and provided protection against excitotoxicity in primary brain cell cultures at micromolar concentrations. Bioassay- guided fractionation of the EtOAc extract led to the isolation of three known sesquiterpenes: acetylvalerenolic acid (1), valerenal (2) and valerenic acid (3), 1 and 3 were active as inhibitors of NF- κ κ κB at a concentration of 100 μg/mL. Acetylvalerenolic acid (1) reduced NF- κ κ κB activity to 4%, whereas valerenic acid (3) reduced NF- κ κ κ B activity to 25%. Copyright © 2006 John Wiley & Sons, Ltd. Keywords: NF-κ B; valerian; traditional (European) medicine; sesquiterpenes; HeLa cells; neurons. Received 2 June 2006 Accepted 16 June 2006 INTRODUCTION Valeriana officinalis L. (Valerianaceae), commonly known as valerian, is probably one of the most popular medicinal herbs used throughout human history. The reputation of this plant in modern rational phytotherapy is mainly due to its pharmacological properties as a mild sedative, and for treating mild nervous tension and temporary sleeping problems. The active com- pounds for these effects, however, remain a matter of great controversy (Bisset and Wichtl, 2001). The inter- est in studying V. officinalis as an inhibitor of NF-κB emerged from the knowledge of its traditional use as an antiinflammatory remedy in Europe and the use of related species in Central America/Mexico for similar purposes (Cáceres, 1999; Mayer, 2003). Therefore, the aim of the present study was to investigate the effects of an EtOAc extract of V. officinalis on neurophy- siological pathologies linked with the NF-κB pathway (Bremner and Heinrich, 2005) and through bioassay- guided fractionation to isolate fractions and compounds from an active EtOAc extract of V. officinalis using the IL-6/luciferase assay as a lead. In particular, the study focused on the potential protective effect of the EtOAc extract against excitotoxicity, which is known to contribute to the pathogenesis of stroke and neurode- generative diseases. MATERIAL AND METHODS Plant material. Rootstock of V. officinalis was com- mercially supplied by Potter’s Herbal Medicines © (Leyland Mill Lane Wigan, Lancs WN1 2SB, UK). Powdered plant material (400 g) was extracted by cold maceration with ethyl acetate (2 L) at room tempera- ture. The solvent was removed under vacuum and dried with a rotavapor to give a total crude extract of 9 g which was stored at -20 °C. Compound 1 (6 mg), acetylvalerenolic acid (acetoxyvalerenic acid), was iso- lated by two different chromatographic techniques: (a) vacuum liquid chromatography on silica gel column * Correspondence to: Professor Michael Heinrich, Centre for Phar- macognosy and Phytotherapy, The School of Pharmacy, University of London, 29–39 Brunswick Square, London WC1N 1AX, UK. E-mail: michael.heinrich@pharmacy.ac.uk † Current address: Departamento de Farmacia, Facultad de Química. Universidad Nacional Autónoma de México, Mexico City, Mexico. ‡ Current address: Faculty of Health and Life Sciences, De Montford University, Leicester, UK. Contract/grant sponsor: Consejo Nacional de Ciencia y Tecnología (CONACyT, México). Contract/grant sponsor: Secretaría de Educación Pública (SEP, México). Contract/grant sponsor: European Union; contract/grant number: Frame- work 5, QLK3-2000-00 463, AINP.