Piperidine alkaloids from Piper methysticum

Dragull, Klaus; Yoshida, Wesley Y.; Tang, Chung-Shih

doi:10.1016/s0031-9422(03)00111-0

Cited by 95 publications

(73 citation statements)

References 15 publications

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“…The underground parts of the Piper methysticum shrub, which contain high quantities of kavalactones (57,58), are used to prepare the kava beverage. However, some kava herbal supplements may contain pipermethystine, which is an ingredient from aerial stem peelings.…”

Section: Human Datamentioning

confidence: 99%

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

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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, ...

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Section: Human Datamentioning

confidence: 99%

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

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“…The traditional aqueous extract is made from the rhizome and contains glutathione, which offers protection against hepatotoxicity (Whitton et al, 2003). Common commercial kavas are made from leaves and stems as well, which contain additional alkaloids with structural features that have been associated with toxic responses (Dragull et al, 2003;Nerurkar et al, 2004). Additionally, adverse drug interactions with kava have been attributed to inhibition of P450 enzymes by components of the extract resulting in increased toxicity of other drugs taken concurrently (Mathews et al, 2002).…”

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confidence: 99%

Pharmacokinetics and Disposition of the Kavalactone Kawain: Interaction With Kava Extract and Kavalactones in Vivo and in Vitro

Mathews¹,

Etheridge²,

Valentine³

et al. 2005

Drug Metab Dispos

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ABSTRACT:Reported adverse drug interactions with the popular herb kava have spurred investigation of the mechanisms by which kava could mediate these effects. In vivo and in vitro experiments were conducted to examine the effects of kava extract and individual kavalactones on cytochrome P450 (P450) and P-glycoprotein activity. The oral pharmacokinetics of the kavalactone, kawain (100 mg/kg), were determined in rats with and without coadministration of kava extract (256 mg/kg) to study the effect of the extract on drug disposition. Kawain was well absorbed, with >90% of the dose eliminated within 72 h, chiefly in urine. Compared with kawain alone, coadministration with kava extract caused a tripling of kawain AUC 0-8 h and a doubling of C max . However, a 7-day pretreatment with kava extract (256 mg /kg/day) had no effect on the pharmacokinetics of kawain administered on day 8. The 7-day pretreatment with kava extract only modestly induced hepatic P450 activities. The human hepatic microsomal P450s most strongly inhibited by kava extract (CYP2C9, CYP2C19, CYP2D6, CYP3A4) were inhibited to the same degree by a "composite" kava formulation composed of the six major kavalactones contained in the extract. K i values for the inhibition of CYP2C9 and CYP2C19 activities by methysticin, dihydromethysticin, and desmethoxyyangonin ranged from 5 to 10 M. Kava extract and kavalactones (<9 M) modestly stimulated P-glycoprotein ATPase activities. Taken together, the data indicate that kava can cause adverse drug reactions via inhibition of drug metabolism.

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“…It was reported that no liver enzymes were elevated in rats with a daily dose of 200 or 500 mg kavalactones/kg for 2 weeks (Singh and Devkota 2003). Dragull et al (2003) suggested that an alkaloid, piperrmethystine, in kava may be toxic to liver cells. It was reported that contents and chemotypes of kavalactones vary among parts, kava varieties and plant ages (Siméoni and Lebot 2002).…”

Section: Raw Materialsmentioning

confidence: 99%

Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents

Wang

Bittenbender

et al. 2013

J Food Sci Technol

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The South Pacific islanders have consumed kava beverage for thousands of years. The quality of kava and kava beverage is evaluated through determination of the content of six major kavalactones including methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin. In this study, we determined contents of kavalactones in and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of five different solvents including hexane, acetone, methanol, ethanol and ethyl acetate. The six major kavalactones were detected in all kava beverages with Jun Wang and Weiyue Qu contributed equally to this work.

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Piperidine alkaloids from Piper methysticum

Cited by 95 publications

References 15 publications

Toxicity of Kava Kava

Toxicity of Kava Kava

Pharmacokinetics and Disposition of the Kavalactone Kawain: Interaction With Kava Extract and Kavalactones in Vivo and in Vitro

Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents

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