Complex effects of aqueous extract of Melampyrum pratense and of its flavonoids on activity of primary cultured hippocampal neurons

^a Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel
^b Center for Neurobiological Research, Perm State Pharmaceutical Academy, Perm, Russia
^c Department of Botany, Perm State Pharmaceutical Academy, Perm, Russia

Received 2 September 2014, Revised 23 December 2014, Accepted 27 January 2015, Available online 2 February 2015

doi:10.1016/j.jep.2015.01.036

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Abstract

Ethnopharmacological relevance

The aqueous extract of the plant Malmpyrum pratense (Mp), is widely used in traditional medicine as a sedative, yet the biological basis of its action is not known.

Aim of the study

The effects of Mp on network activity and intrinsic and synaptic properties were studied in cultured hippocampal neurons in an attempt to analyze its mode of action.

Materials and methods

Dissociated cultures of rat hippocampal neurons were used. Spontaneous network activity was assessed by variations in intracellular [Ca²⁺] concentrations, reflecting action potential discharges. Individual neuronal synaptic activity was measured by patch clamp recordings from similar neurons. The effect of exposure to different concentrations of Mp and some of its main ingredients was measured.

Results

Mp produced complex, dose dependent, reversible effects on network activity, increasing it with low concentrations, and decreasing it at high concentrations. Individual flavonoids contained in Mp mimicked the effects of the extract, both for the facilitating and suppressing effects of the extract. Electrophysiologically, Mp caused a reduction in spontaneous activity, but did not affect membrane properties of individual patch clamped neurons, nor did it affect mEPSCs recorded from these neurons. However, a transient increase in reactivity to pulse application of GABA was evident.

Conclusions

These results suggest that a main sedative effect of Mp is on GABAergic neurotransmission in cultured hippocampal neurons.

Graphical abstract

Abbreviations

sIPSC, spontaneous inhibitory postsynaptic currents;
mEPSC, miniature excitatory postsynaptic currents;
TTX, tetrodotoxin

Keywords

Melampyrum pretense;
Hippocampal culture;
Flavonoids;
Calcium imaging;
Network bursts;
GABA

: Corresponding author. Tel.: +972 89342557; fax: +972 89344140.

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