title: Lignans isolated from valerian: identification and characterization of a new olivil derivative with partial agonistic activity at A(1) adenosine receptors.
abstract: A methanolic extract of the roots of Valeriana officinalis (valerian) was investigated for its lignan content. In addition to the lignans 8'-hydroxypinoresinol (1) and pinoresinol-4-O-beta-D-glucoside (2), which had already been isolated from valerian in an earlier study, the 7,9'-monoepoxylignans massoniresinol-4'-O-beta-D-glucoside (3), 4'-O-beta-D-glucosyl-9-O-(6' '-deoxysaccharosyl)olivil (4), and berchemol-4'-O-beta-D-glucoside (5) and the 7,9':7',9-diepoxylignans pinoresinol-4,4'-di-beta-O-D-glucoside (6), 8-hydroxypinoresinol-4'-O-beta-D-glucoside (7), and 8'-hydroxypinoresinol-4'-O-beta-D-glucoside (8) were identified. While lignans 3, 6, 7, and 8 had already been isolated from other plants, lignans 4 and 5 are new natural products. The lignans were investigated in radioligand binding assays at various receptors of the central nervous system, including GABA(A), benzodiazepine, 5-HT(1A), and adenosine A(1) and A(2A) receptors, to investigate their potential contribution to the pharmacological activity of valerian. The novel olivil derivative 4 proved to be a partial agonist at rat and human A(1) adenosine receptors exhibiting A(1) affinity and activity in low micromolar to submicromolar concentrations. Lignan 4 is the first nonnucleoside adenosine receptor agonist not structurally related to adenosine.
authors.affiliation: Pharmaceutical Institute Poppelsdorf, University of Bonn, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Schumacher
authors.forename: Silke
authors.initials: S
authors.lastname: Scholle
authors.forename: Josef
authors.initials: J
authors.lastname: Hölzl
authors.forename: Nasser
authors.initials: N
authors.lastname: Khudeir
authors.forename: Sonja
authors.initials: S
authors.lastname: Hess
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D058787:GABA-A Receptor Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D014632:Valerian / Q000737:chemistry*
chemical_list: D058787:GABA-A Receptor Antagonists; D017705:Lignans; D058906:Purinergic P1 Receptor Agonists; D012702:Serotonin Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000242:Cyclic AMP