The Antinociceptive Actions of Kava Components in Mice

Jamieson, Dara G.; Duffield, P.H.

doi:10.1111/j.1440-1681.1990.tb01349.x

Cited by 98 publications

(47 citation statements)

References 24 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When kavalactones were tested individually, they did not exhibit biological activity similar to that found in the whole kava extract. On the other hand, the recombined kavalactones exhibited biological activity found with the entire kava extract (5,13,24).…”

Section: Biological Effectsmentioning

confidence: 97%

“…Jamieson and Duffield (24) determined that the lipid soluble extract (kava resin) orally administered to male Balb/c mice had a LD 50 of 700 mg/kg and above, with the death due to respiratory failure. The acute toxicity values LD 50 (mg/kg) of the six major kavalactones in mice, dogs, cats, and rabbits were determined and the results are summarized in Table 1 (NLM, 1998).…”

Section: Animal Datamentioning

confidence: 99%

“…Ethanol and the lipid soluble extract (kava resin) greatly increased each other's hypnotic action in mice. Interaction of kava and alcohol has important clinical and social consequences, since kava is usually taken together with alcoholic drinks (24). However, Anke et al (44) determined that the four kavalactones, kawain, methysticin, yangonin and desmethoxyyangonin, did not inhibit alcohol dehydrogenase in vitro, suggesting that interaction of kavalactones with alcohol does not involve alcohol dehydrogenase inhibition.…”

Section: Animal Datamentioning

confidence: 99%

See 2 more Smart Citations

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

View full text Add to dashboard Cite

Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity. KeywordsKava; anti-anxiety herbal beverage; top-selling botanical; hepatotoxicity; metabolism; mechanism Kava, prepared from the rhizome of the kava tropical shrub plant, Piper methysticum Forst F., is a traditional beverage used for many centuries, especially at ceremonial activities in the South Pacific (1-6). During recent years, kava has been used in Europe for treatment of anxiety and nervous disorders such as stress and restlessness, and in the United States as a natural alternative to anti-anxiety drugs and sleeping pills (6). Kava sales totaled more than $ 100 million in 1998, being the fifth leading seller of the North American botanicals (7).The association between the use of kava products and hepatotoxicity has prompted many countries, including Germany, Switzerland, France, Canada, and the United Kingdom, to take regulatory actions, ranging from warning consumers to removing kava-containing products from the marketplace. On March 25, 2002, the Center for Food Safety and Applied Nutrition (CFSAN), U.S. Food and Drug Administration (FDA) issued a Consumer Advisory entitled "Kava-containing dietary supplements may be associated with severe liver injury" to the public (8, 9). Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it Address correspondence to Peter P. Fu, National Center for Toxicological Research, Jefferson, AR 72079. peter.fu@fda.hhs.gov; chanp@niehs.nih.gov. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript was banned in Germany, France, Switzerland, Australia, and Canada (10). In this review, human exposure and metabolism of kava are briefly addressed, recent findings on the toxicity of kava are reported, and possible mechanisms by which kava induces toxicity are described. CHEMICAL COMPOSITIONThe kava plant, belonging to the Piperacae family, is widely cultivated in the South Pacific.Kava is cultivated for its rootstock. Depending upon the amount of kavalactones contained in the resin, the rootstock shows different color, varying from white to dark yellow (2,5,6). Fresh kava rootstock contains about 80% water. Dried rootstock consists of about 43% starch, 20% fibers, 12% water, 3-4% proteins, 3% sugars, 3% minerals, ...

show abstract

Section: Biological Effectsmentioning

confidence: 97%

Section: Animal Datamentioning

confidence: 99%

Section: Animal Datamentioning

confidence: 99%

See 1 more Smart Citation

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

View full text Add to dashboard Cite

show abstract

“…Investigations of kava preparations have demonstrated several biological activities. [3][4][5][6] Preparations are used in Europe and North America to manage mild anxiety disorders.…”

mentioning

confidence: 99%

“…Investigations of kava preparations have demonstrated several biological activities. [3][4][5][6] Preparations are used in Europe and North America to manage mild anxiety disorders. 6) Chemical investigations of kava have led to the isolation and characterization of 19 styryl-a-pyrones (kavalactones) which are believed to be responsible for the pharmacological activities.…”

mentioning

confidence: 99%

Microbial Metabolism. Part 5. Dihydrokawain

Herath

Ferreira

Mikell

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Piper methysticum FORST (Piperaceae) is a South Pacific plant used as an intoxicating beverage by the natives.2) It is commonly referred to as kava-kava or kava. Investigations of kava preparations have demonstrated several biological activities. [3][4][5][6] Preparations are used in Europe and North America to manage mild anxiety disorders.6) Chemical investigations of kava have led to the isolation and characterization of 19 styryl-a-pyrones (kavalactones) which are believed to be responsible for the pharmacological activities.8) The most abundant of these lactones are desmethoxyyangonin, yangonin, dihydrokawain, kawain, dihydromethysticin and methysticin. 9)Centuries of use of kava-kava by the South Pacific islanders showed no serious health risks. The standardized extracts of kava-kava prepared in Europe on the other hand had been shown to cause hepatotoxic effects. 10) This has been attributed to differences in the extraction procedures. Traditionally, the kava-extracts are prepared by macerating the roots of P. methysticum with water and coconut milk.11) This procedure extracts kava lactones and glutathione in a 1 : 1 ratio.12) In the standard extraction method the use of 60% aqueous ethanol or acetone results in a kava lactone concentration of over 30 times that found in the traditional extracts. It has been suggested that the resulting high concentration of lactones could saturate the detoxification pathways leading to hepatotoxicity. In addition, such extracts do not contain the tripeptide, glutathione, which plays a major role in the conversion of lactones into excretable products. 12) In another study which has demonstrated the formation of electrophilic quinoid metabolites when kava was incubated in vitro with hepatic microsomes, has led to the suggestion that the production of these quinoids might contribute towards hepatotoxicity in humans when metabolic pathways are altered. 13)To evaluate the safety and efficacy of kava, knowledge of how its active constituents are metabolized is important. One such investigation 14) led to the detection of human urinary metabolites of the kava lactones following the consumption of kava prepared by the traditional method. Transformations observed were the reduction of the enolic 3,4-double bond and/or demethylation of the 4-methoxy group. In rat, however, in addition to metabolism occurring at the aromatic ring to form phenolic products, compounds resulting from the cleavage of the 5,6-dihydro-a-pyrone ring had been observed. 15) In both cases, unconverted kava lactones were detected in high concentrations.The importance of using microbial models to generate mammalian metabolites of biologically active compounds is well documented.16) The quantities of metabolites are usually sufficient to carry out complete structure elucidations and further pharmacological evaluations. The metabolites can furthermore be used as standards for detection in biological fluids. In the mammalian experiments cited above, the absence of such standards has led to the proposition of tent...

show abstract

Psychoactive Herbs in Veterinary Behavior Medicine

Schwartz¹

2005

View full text Add to dashboard Cite

The Antinociceptive Actions of Kava Components in Mice

Cited by 98 publications

References 24 publications

Toxicity of Kava Kava

Toxicity of Kava Kava

Microbial Metabolism. Part 5. Dihydrokawain

Psychoactive Herbs in Veterinary Behavior Medicine

Contact Info

Product

Resources

About