Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [³H]Glutamate Binding to Rat Synaptic Membranes

Abstract

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [3H]Glutamate. Aqueous valerian extract increased [3H]Glutamate binding from 1 × 10−7 to 1 × 10−3 mg/mL. In the presence of (2S,1′S,2′S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2′R,3′R)-2-(2′,3′-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [3H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [3H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [3H]Glutamate binding after 1.6 × 10−2 mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.

The anxiolytic effects of a Valerian extract is based on Valerenic acid

“…Moreover, VE and VA also interact with glutamate receptors, from which an anxiolytic effect can also be induced [18]. For both of the latter reports confirmation from in-vivo conditions is not as yet available.…”

<b><i>Valeriana officinalis</i></b> Root Extract Modulates Cortical Excitatory Circuits in Humans

“…Other studies indicate that VE has antioxidant and neuroprotective effects [6,7,8,9]. Furthermore, VE modulates brain neurotransmitters [10,11,12,13,14], and shows antianxiety, antidepressant, and antiepileptic activity in animal models [15,16]. …”

Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade

“…In the same study, kainate-induced cell death was marginally decreased only, suggesting the selective effect of RRV on NMDA-R over other glutamate receptor subtypes [52]. Receptor selectivity of RRV was further studied using its water extract and known constituents in rat cortical membranes [54]. Activity of RRV on glutamate receptor subtypes was complicated by dose-dependent variations.…”

“…Activity of RRV on glutamate receptor subtypes was complicated by dose-dependent variations. While RRV was inactive against the AMPA receptor, glutamate binding to NMDA-R was increased by a high concentration (10 mg/mL) of the RRV water extract [54]. Conversely, glutamate binding to kainate receptor was decreased by a low RRV concentration (0.05 mg/mL) [54].…”

“…While RRV was inactive against the AMPA receptor, glutamate binding to NMDA-R was increased by a high concentration (10 mg/mL) of the RRV water extract [54]. Conversely, glutamate binding to kainate receptor was decreased by a low RRV concentration (0.05 mg/mL) [54]. The findings could be interpreted as a dual effect of RRV on different glutamate receptor subtypes—varied results on metabotropic glutamate receptors added to the complication [54].…”