Interaction of Various Piper methysticum Cultivars with CNS Receptors in vitro

Abstract

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 (mu and delta), 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 micrograms/ml, whereas root extracts were less active with IC50 values ranging from 5 micrograms/ml (Nene) to 87 micrograms/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 (mu and delta) and histamine (H1 and H2) receptors more potently than the corresponding root extracts with IC50 values ranging from 1 to 100 micrograms/ml vs. > or = 100 micrograms/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 (mu and delta) 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.

Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava‐kava)

“…For example, synthetic as well as herbal 5-HT 3 antagonists like Zingiber officinale can also exert anxiolytic effects without interfering with the performance on learning tasks (Buhot et al, 2000;Hasenöhrl et al, 1998). This is interesting in the light of recent evidence showing that kavapyrones can directly interact with central 5-HT receptive sites (Dinh et al, 2001;Grunze et al, 2001), which are considered to play a crucial role in the neural control of emotion and associative processes (Meneses, 1999).…”

Extracts of kava ( Piper methysticum ) induce acute anxiolytic-like behavioral changes in mice

“…Kava's anticonvulsant properties have been linked to its interaction with the voltage-gated sodium and calcium channels (Gleitz et al 1996;Maura et al 1997;Friese and Gleitz 1998;Schirrmacher et al 1999). Kava's anxiety-reducing effects have been suggested to be due to its interactions with the GABA A receptor; however, data supporting this conjecture are equivocal (Davies et al 1992;Jussofie et al 1994;Boonen and Häberlein 1998;Dinh et al 2001). Other studies have indicated that kava extracts and kava lactones may alter several neurochemical systems (Seitz et al 1997;Baum et al 1998;Feger et al 1998;Dinh et al 2001); however, none of these actions have been associated with specific behavioral effects in vivo.…”

Desmethoxyyangonin and Dihydromethysticin Are Two Major Pharmacological Kavalactones With Marked Activity on the Induction of Cyp3a23

“…These kavalactones include desmethoxyyangonin (DMY), dihydrokawain, dihydromethysticin (DMS), kawain, methysticin, and yangonin. The relative abundance of the kavalactones varies markedly among different parts of the plant and also depends on where the plant grows (Singh and Blumenthal, 1997;Dinh et al, 2001). Structurally, the active kavalactones exist as the (ϩ) isomer, and all kavalactones contain a benzene ring and a methoxy lactone connected via an ethyl or ethylene bridge (Dharmaratne et al, 2002).…”