© Georg Thieme Verlag Stuttgart · New York
Interaction of Various Piper methysticum Cultivars with CNS Receptors in vitro
June 6, 2000
October 29, 2000
31 December 2001 (online)
Methanolic leaf and root extracts of the Hawaiian kava (Piper methysticum Forst.) cultivars, Mahakea, Nene, Purple Moi and PNG, were tested on binding affinities to CNS receptors including GABAA (GABA and benzodiazepine binding site), dopamine D2, opioid (μ and δ), serotonin (5-HT6 and 5-HT7) and histamine (H1 and H2). HPLC analysis was carried out in order to determine the amount of the main kavalactones kavain, 7,8-dihydrokavain, methysticin, 7,8-dihydromethysticin, yangonin and 5,6-demethoxyyangonin. The most potent binding inhibition was observed for leaf extracts to GABAA receptors (GABA binding site) with IC50 values of approximately 3 μg/ml, whereas root extracts were less active with IC50 values ranging from 5 μg/ml (Nene) to 87 μg/ml (Mahakea). Since the leaf extracts generally contained lower amounts of the kavalactones than the root extracts, there might exist additional substances responsible for these activities. Leaf extracts also inhibited binding to dopamine D2, opioid (μ and δ) and histamine (H1 and H2) receptors more potently than the corresponding root extracts with IC50 values ranging from 1 to 100 μg/ml vs. ≥ 100 μg/l, respectively. Significant differences in the potential of binding inhibition were also observed between cultivars. Binding to serotonin (5-HT6 and 5-HT7) and benzodiazepine receptors was only weakly inhibited by both root and leaf extracts of all four cultivars. In conclusion, our investigation indicates that the GABAA, dopamine D2, opioid (μ and δ) and histamine (H1 and H2) receptors might be involved in the pharmacological action of kava extracts. Since the cultivars contained similar amounts of kavalactones, while their pharmacological activities differed markedly, other constituents may play a role in the observed activities. Additionally, leaves generally exhibited more potent binding inhibition than roots, therefore leaf of P. methysticum might be an interesting subject for further pharmacological studies.
BHK:baby hamster kidney
CHO:Chinese hamster ovary
CNS:central nervous system
3H-LSD:3 H-lysergic acid diethylamide
HPLC:high performance liquid chromatography
IC50:50 % inhibitory concentration
SFV:Semliki Forest Virus
Piper methysticum - Piperaceae - leaf extracts - root extracts - styryl pyrones - cultivars - CNS recombinant receptors
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Dr. Urs Simmen
Institute of Pharmaceutical Biology
University of Basel
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Phone: ++41 61 721 52 16