Interaction of various Piper methysticum cultivars with CNS receptors in vitro

Methanolic leaf and root extracts of the Hawaiian kava (Piper methysticum F orst.) cultivars, Mahakeo, Nene, Purple Moi and PNC, were tested on binding affinities to CNS receptors including GABA(A) (GABA and benzodiazepine bin ding site), dopamine D-2, opioid (mu and delta), serotonin (5-HT6 and 5-HT7 ) and histamine (H-1 and H-2). HPLC analysis was carried out in order to de termine the amount of the main kavalactones kavain, 7,8-dihydrokavain, meth ysticin, 7,8-dihydromethysticin, yangonin and 5,6-demethoxyyangonin. The mo st potent binding inhibition was observed for leaf extracts to GABA(A) rece ptors (GABA binding site) with IC50 values of approximately 3 mug/ml, where as root extracts were less active with IC50 values ranging from 5 mug/ml (N ene) to 87 mug/l (Mahakea). Since the leaf extracts generally contained low er amounts of the kavalactones than the root extracts, there might exist ad ditional substances responsible for these activities. Leaf extracts also in hibited binding to dopamine D-2, opioid (mu and delta) and histamine (H-1 a nd H-2) receptors more potently than the corresponding root extracts with I C50 values ranging from 1 to 100 mug/ml vs. greater than or equal to 100 mu g/l, respectively. Significant differences in the potential of binding inhi bition were also observed between cultivars. Binding to serotonin (5-HT6 an d 5-HT7) and benzodiazepine receptors was only weakly inhibited by both roo t and leaf extracts of all four cultivars. In conclusion, our investigation indicates that the GABA(A), dopamine D-2, opioid (mu and delta) and histam ine (H-1 and H-2) receptors might be involved in the pharmacological action of kava extracts. Since the cultivars contained similar amounts of kavalac tones, while their pharmacological activities differed markedly, other cons tituents may play a role in the observed activities. Additionally, leaves g enerally exhibited more potent binding inhibition than roots, therefore lea f of P. methysticum might be an interesting subject for further pharmacolog ical studies.