Kava lactones

R. M. Smith, O. Chienthavorn, I. D. Wilson, B. Wright, and E. M. Lenz, Superheated water chromatography-nuclear magnetic resonance spectroscopy of kava lactones, Phytochem. Anal. 16 (2005), 217-221. 

The active constituents are resinous compounds called kava lactones. The exact mechanism of action is unclear though it is thought to act on GABA receptors resulting in the sedative effects. 

In animal studies, kava lactones decreased muscle action potentials and disrupted voltage-gated Na channels. In vitro, kava was found to block... 

Key Words Piper methysticunr, kava lactones anxiolytic hypnotic. 

The neurological effects of kava are attributed to a group of substituted dihydropyrones called kava lactones (1). The main bioactive constituents include yangonin, desmethoxyyangonin, 11-methoxyyangonin, kavain (kawain), dihydrokavain, methysticin, dihydromethysticin, and 5,6-dehydromethysticin (8). It is believed that the components present in the lipid-soluble kava extract, or kava resin, are responsible for the central nervous system (CNS) activities of kava including sedation, hypnosis, analgesia, and muscle relaxation (9). Aqueous kava extract was not active orally in mice or rats. 

As mentioned in Section 4.1, kava is a centrally acting skeletal muscle relaxant. The kava lactones kavain, dihydrokavain, methysticin, and dihydromethysticin isolated from kava rootstock were shown to antagonize strychnine-induced convulsions in mice (20). 

Several kava lactones have been identified in human urine samples after ingestion of a kava beverage prepared from a commercial 450-g sample of P. methysticin extracted with 3 L of room temperature water (31). Observed metabolic transformations include reduction of the 3,4 double bond and/or demethylation of the 4-methoxyl group on the a-pyrone ring system. Demethylation of the 12-methoxy substituent in yangonin and hydroxylation at carbon 12 of desmethoxyyangonin have also been observed. Chemical structures for these kava components and metabolites can be seen in the cited reference. 

A number of natural products have been extracted by SFE. Roots are a typical matrix from which several compounds are extracted. This is the case for the extraction of baicalein and baicalin from Scutellaria root (22), active compounds from lovage roots (23), tanshinone IIA from Salvia mil-tiorrhiza bunge (24), and kava lactones from kava roots (25). In all of these cases, the use of pure CO2 as extractant was the best option, as the extraction efficiency did not increase using organic-solvent-modified CO2 as extractant. 

Ashraf-Khorassani M, Taylor LT, Martin M. Supercritical fluid extraction of kava lactones from kava root and their separation via supercritical fluid chromatography. Chromatographia 1999 50 287-292. 

Smith, R.M., Thakrar, H., Arowolo, T.A. and Shafi, A.A. (1984) High performance liquid chromatography of kava lactones from Piper methysticum. Journal of Chromatography, 283, 303—308. 

Smith, R.M. (1983) Kava lactones in Piper methysticum from Fiji. Phytochemistry, 22(4), 1055 1056. 

Akasu, M., Itokawa, H. and Fujita, M. (1974) Four new fluorescent components isolated from the callus tissue of Stephania cepharantha. Tetrahedron Letters, 41, 3609—3612. Ashraf-Khorassani, M., Taylor, L.T. and Martin, M. (1999) Supercritical fluid extraction of Kava lactones from Kava root and their separation via supercritical fluid chromatography. Chromatographia, 50, 287—292. 

Lopez-Avila, V. and Benedicto, J. (1997) Supercritical fluid extraction of kava lactones from Piper methysticum (kava) herb. HRC-J ournal ofHigh Resolution Chromatography, 20, 555—559. Macierewicz, Z. (1950) Synthesis of the lactone of the mother substance of yangonin. Roczniki Chemique, 24, 144—166. 

Rasmussen etal. (1979) attempted to measure by gas chromatography the n-octanol-water partition coefficients of the major kava lactones and found that these compounds could not be detected in the aqueous phase. Since the bulk of the earlier pharmacological work had concentrated on the water-soluble lactones, Buckley etal. (1979) investigated the biological activity of the water-soluble fiactions of kava obtained by steam distillation. They found that the fractions so obtained contained biologically active materials that were relatively free of any lactones. These materials suppressed spontaneous activity in... 

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