PhD, University of Geneva
Epilepsy is a chronic brain disorder characterised by recurrent seizures. It is the most prevalent neurological disease worldwide, with over 70 million people afflicted. Despite the availability of over 25 approved anti-epileptic drugs, a third of treated epilepsy patients experience serious side effects to these medications, and another third does not respond at all and are referred to as being “pharmacoresistant”. Thus, there is a clear need for new AEDs. Today, medicinal plants still provide efficient treatments for people in needs. In this frame, we investigated several plants used locally for their anticonvulsant properties. In this work, our challenge is to support traditional knowledge by adding scientific experiments into it. Thus, we try to target and isolate the active compounds from plants used around the world for their anti-epileptic properties. For this, we are using chemistry instruments coupled to an innovative in vivo model to identify, target, and isolate the bioactive compounds. This work could lead to new treatments for therapy resistant epileptic patients but also to supplement and improve existing treatments.
Abstract: Extracts from rhizomes of Cyperus articulatus L. (Cyperaceae) used in Africa and Amazonia to treat many diseases has been shown to possess sedative and anticonvulsant properties. The aim of this study is to determine the mechanism of action of Cyperus articulatus extracts. In Xenopus oocytes expressing receptors, using electrophysiological measurement, extracts of rhizomes of Cyperus articulatus (300 microg/ml) inhibited 50% of the EC(50) and EC(80) of glutamate (1.3 and 2.9 microM, respectively) induced inward current through hNMDAR1A/2A receptors. Extracts induced very small current through rGluR3 receptors. The largest current induced by the extract (30 mg/ml) represents 128% of the EC(100) of glutamate induced inward current, through rGluR3 receptors. The excess 28% current could be induced by aspartate and/or glutamate in the extracts. The effect on Xenopus oocytes expressing heteromeric GABA(B)R1b/R2 receptors and rectifying potassium channels (Kir3) is clear. A decoction and water extract of Cyperus articulatus induced a large inward current that represented 71 and 57% (respectively) of the EC(100) of gaba (30 microM) induced inward current. The water extract induced also a large current through rectifying potassium channels (Kir3). Part of the current induced through GABA(B) receptors could be related to rectifying potassium channels and GABA(B) site receptors. Cyperus articulatus extracts possessed components that could decrease excitation (NMDA receptor antagonists) and increase inhibition (GABA(B) receptor agonists) in the central nervous system.
Pub.: 28 Oct '04, Pinned: 27 Jul '17