Lignans isolated from Valerian:: Identification and characterization of a new olivil derivative with partial agonistic activity at A1 adenosine receptors

A methanolic extract of the roots of Valeriana offlicinalis (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)oliviI (4), and berchemol-4'-O-beta-D-glucoside (5) and the 7,9':7',9-diepoxylignans pinoresinol-4,4'-di-beta-D-glucoside (6), 8-hydroxypinoresinol-4'-O-PD-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-HT1A, 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, affinity and activity in low micromolar to submicromolar concentrations. Lignan 4 is the first nonnucleoside adenosine receptor agonist not structurally related to adenosine.