doi: 10.1155/2015/617620

Milan Fedurco,1 Jana Gregorová,2 Kristýna Šebrlová,2 Jana Kantorová,2
Ondlej Peš,2 Roland Baur,3 Erwin Sigel,3 and Eva Táborská2
1Michelin Recherche et Technique S.A., Route Andr´e-Piller 30, 1762 Givisiez, Switzerland
2Department of Biochemistry, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic
3Institute of Biochemistry and Molecular Medicine, University of Bern, B¨uhlstrasse 28, 3012 Bern, Switzerland
Correspondence should be addressed to Milan Fedurco; milan.fedurco@gmail.com
Received 28 July 2015; Revised 5 September 2015; Accepted 15 September 2015
Academic Editor: Emanuel Strehler

• Published online 2015 Oct 5

Abstract

The California poppy (Eschscholzia californica Cham.) contains a variety of natural compounds including several alkaloids found exclusively in this plant. Because of the sedative, anxiolytic, and analgesic effects, this herb is currently sold in pharmacies in many countries. However, our understanding of these biological effects at the molecular level is still lacking. Alkaloids detected in E. californica could be hypothesized to act at GABA_A receptors, which are widely expressed in the brain mainly at the inhibitory interneurons. Electrophysiological studies on a recombinant α ₁ β ₂ γ ₂ GABA_A receptor showed no effect of N-methyllaurotetanine at concentrations lower than 30 μM. However, (S)-reticuline behaved as positive allosteric modulator at the α ₃, α ₅, and α ₆ isoforms of GABA_A receptors. The depressant properties of aerial parts of E. californica are assigned to chloride-current modulation by (S)-reticuline at the α ₃ β ₂ γ ₂ and α ₅ β ₂ γ ₂ GABA_A receptors. Interestingly, α ₁, α ₃, and α ₅ were not significantly affected by (R)-reticuline, 1,2-tetrahydroreticuline, codeine, and morphine—suspected (S)-reticuline metabolites in the rodent brain.

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1. Introduction

The California poppy is known in folk medicine for its sedative, anxiolytic, and antinociceptive effects [1–4]. These effects have been traditionally assigned to protopine and allocryptopine (see Figure 1). Both alkaloids act as weak stimulators of the binding of GABA_A receptor agonists in the rat brain [5, 6], as anti-inflammatory agents [7] and as acetylcholinesterase inhibitors [7, 8]. Another aporphine alkaloid isolated from this plant, namely, N-methyllaurotetanine (NMT), was reported to act as antagonist at the serotonin 5HT_1AR receptor (EC₅₀ = 155 nM, K _i = 85 nM) [9]. Protopine and allocryptopine were also found to block human serotonin and noradrenaline transporters (hSERT and NERT) and possess antidepressant-like effects on animal models [10]. However, it is not clear whether typical pharmacy preparations (i.e., 300 mg of dry plant material per capsule) contain sufficient quantities of these alkaloids required to induce desired biological effects. Even though the presence of NMT in this plant has been clearly established, its content in the aerial parts of this perennial herb is currently unknown. Furthermore, it is not known whether or not this molecule interacts with the GABA_A receptor.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609799/