Lignans Isolated from Valerian:  Identification and Characterization of a New Olivil Derivative with Partial Agonistic Activity at A₁ 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.

Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro

“…Initial radioligand binding studies were performed by MDS Pharma Services (Bothell, WA) as previously described for serotonin receptor subtypes 1A, 1B, 2B, 2C, 3, 5A, 6, 7, serotonin transporter [5,6,8,23,31,32,[37][38][39][40][41][43][44][45]47]. Significant binding affinity was only observed at the 5-HT 5a receptor (>50%) for the PE and DCM extracts at a concentration of 50 μg/ml [12].…”

“…Currently, there is no scientific agreement on the mechanism of action of valerian's sedating activity or the compounds responsible. Many potential mechanisms for the pharmacological activity of valerian have been proposed, including agonistic activities on the GABA, adenosine, barbiturate, and benzodiazepine receptors [34,40,46]. However, the concentrations used in these investigations were extremely high in the older reports and more recent reports put some of these data into question [12,40].…”

The rat adenine receptor: pharmacological characterization and mutagenesis studies to investigate its putative ligand binding site

“…Coexpression of the wt rAdeR, or its mutants, respectively, with mammalian G i proteins allowed the performance of [ 35 S]GTPγS binding studies, which can indicate the degree of receptor activation [42][43][44]. As already mentioned, G proteins can allosterically modulate the binding of an agonist to its receptor.…”

“…Four injections were performed before serum collection. To gain better specificity, additional antibodies were raised against the following peptides: [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] (N-term), 181-194 (extracellular loop 2 (ECL2)), 222-235 (intracellular loop 3 (ICL3)), 295-314 (C-terminal), and 313-331 (C-terminal). These antibodies were produced in two rabbits each by Thermo Scientific.…”

A New Neolignan Glycoside from the Leaves of Acer truncatum

“…During our ongoing investigations into the chemical constituents of this plant, the new neolignan glycoside (7R,8R)-7,8-dihydro-9′-hydroxyl-3′-methoxyl-8-hydroxymethyl-7-(4-hydroxy-3-methoxyphenyl)-1′-benzofuranpropanol 9′-O-β-Dglucopyranoside (1) and eight known compounds: (7R,8R)-7,8-dihydro-9′-hydroxyl-3′-methoxyl-8-hydroxymethyl-7-(4-O-α-L-rhamnopyranosyloxy-3-methoxyphenyl)-1′-benzofuranpropanol (2), schizandriside (3), lyoniresinol (4), berchemol (5), (-)-pinoresinol-4-O-β-D-glucopyranoside (6), hecogenin (7), chlorogenic acid (8) and neochlorogenic acid (9) were isolated from a water extract of A. truncatum leaves. The identification of the known compounds was supported by comparison with published data of related compounds [5][6][7][8][9][10][11][12]. Compounds 1-7 were evaluated for their antibacterial activities against Escherichia coli, Staphylococcus aureus, Micrococcus luteus and Bacillus cereus.…”