Abstracts

Botanicals such as valerian and passionflower are commonly used by epilepsy patients and may have some anticonvulsant effects. In mouse models, [italic]Passiflora [/italic]extracts have been shown to have anxiolytic effects and inhibit pentylenetetrazol (PTZ)-induced seizures. Active ingredients are presumed to be flavonoids. Many flavonoids interact with benzodiazepine receptors, and the flavonoids chrysin and hispiduline have been found to inhibit PTZ-induced seizures in rodent models. The flavonoid content of commercial extracts from [italic]Passiflora incarnata [/italic]whole herb was analyzed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC).
The WSP2 strain of mice, which are genetically prone to handling-induced convulsions (HIC), was used to test for anticonvulsant effects of the extracts. HIC were assessed at 30 minutes, 1 hour, 2 hours and 4 hours after a single i.p. injection.
The effects of the extracts on GABAergic neurotransmission were examined with voltage-clamp recordings from CA1 pyramidal cells in acutely prepared rat hippocampal slices in the presence of the glutamate receptor antagonist kynurenic acid (1 mM). A total of 14 different flavonoid peaks were detected with a total flavonoid content of 2.7% in one of the extracts.
Handling-induced convulsions in WSP2 mice were inhibited at a dosage of 1000 mg/kg of whole [italic]Passiflora[/italic] extract beginning 30 minutes to 1 hour after i.p. injection.
Application of [italic]Passiflora[/italic] extract to hippocampal slices generated inhibitory currents in voltage-clamped (V[sub]h [/sub]= -30mV) CA1 pyramidal cells in a dose dependent fashion beginning at 100[mu]g/ml. The extract induced inhibitory current was abolished by application of the GABA[sub]A[/sub] receptor selective antagonist, GABAzine (20 [mu]M). Whole [italic]Passiflora[/italic] extracts show anticonvulsant action in seizure-prone WSP2 mice, and induce a GABA[sub]A[/sub] receptor-mediated current in hippocampal CA1 pyramidal cells.
If, as presumed, flavonoids are the active ingredient of [italic]Passiflora[/italic], the dosages of 1000 mg/kg in WSP2 mice and of 100 [mu]g/ml in hippocampal slices would correspond to 27 mg/kg and 2.7 [mu]g/ml of flavonoids which would be pharmacologically relevant.
Further studies are needed to determine the actual active ingredients and pharmacological mechanisms and to evaluate any potential clinical significance of these findings. (Supported by fellowships to SME and AS from the NIH/NCCAM funded Oregon Center for Complementary and Alternative Medicine in Neurological Disorders, a fellowship to DJR from the Burroughs Wellcome Fund, and by a K23 grant to SME by NIH NCCAM. [italic]Passiflora[/italic] extracts were kindly provided by Oregon[apos]s Wild Harvest, Sandy, Oregon/USA and by Weleda Inc., Arlesheim/Switzerland. WSP2 mice were kindly provided by the laboratory of J. Crabbe, PhD at the VAMC and Oregon Health and Science University, Portland, Oregon.)