Kavalactone

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The general structure of the kavalactones, without the R1-R2 -O-CH2-O- bridge and with all possible C=C double bonds shown.

Kavalactones are a class of lactone compounds found in the kava shrub. Kavalactones have a wide variety of effects including amnestic, analgesic, anticonvulsant, anxiolytic, nootropic, and sedative/hypnotic activity caused by numerous interactions with the central nervous system via a myriad of mechanisms.

Enzyme inhibition[edit]

Kava extract has been shown to potently inhibit a wide range of hepatic enzymes, suggesting a very high potential for interactions with many pharmaceuticals and herbal medications.[1] For this reason, kava should never be consumed without the permission of a primary care physician, psychiatrist, and/or any other doctor who is prescribing medication for a patient. It is also recommended that potential users discuss their kava use with a pharmacist. If undergoing anesthesia, it is recommended to note any use of kava well in advance of any surgery. Patients may be instructed to temporarily discontinue use of kava for a set period of time before and after the surgery.

Toxicity[edit]

Several kavalactones (e.g.Methysticin and Yangonin) have been reported to be toxic and/or carcinogenic, although further research into these mechanisms is needed and it is not yet known if kava consumption induces toxic/carcinogenic effects in vivo. Despite this, hepatoxicity has been reported in a small portion of previously healthy kava users.[2][3]

Numerous kavalactones have apoptotic effects on various human tissues, which may be involved in some of the purported toxic effects of kava use.[4][5][6]

Compounds[edit]

See also: Flavokavain

At least 18 different kavalactones have been identified to date, with methysticin being the first identified.[7] Multiple analogues, such as ethysticin, have also been isolated.[8] Some consist of a substituted α-pyrone as the lactone while others are partially saturated.

Name Structure R1 R2 R3 R4
Yangonin 1 -OCH3 -H -H -H
10-methoxyyangonin 1 -OCH3 -H -OCH3 -H
11-methoxyyangonin 1 -OCH3 -OCH3 -H -H
11-hydroxyyangonin 1 -OCH3 -OH -H -H
Desmethoxyyangonin 1 -H -H -H -H
11-methoxy-12-hydroxydehydrokavain 1 -OH -OCH3 -H -H
7,8-dihydroyangonin 2 -OCH3 -H -H -H
Kavain 3 -H -H -H -H
5-hydroxykavain 3 -H -H -H -OH
5,6-dihydroyangonin 3 -OCH3 -H -H -H
7,8-dihydrokavain 4 -H -H -H -H
5,6,7,8-tetrahydroyangonin 4 -OCH3 -H -H -H
5,6-dehydromethysticin 5 -O-CH2-O- -H -H
Methysticin 7 -O-CH2-O- -H -H
7,8-dihydromethysticin 8 -O-CH2-O- -H -H
Kavalactones: General structures
Structure 1
Structure 2
Structure 3
Structure 4
Structure 5
Structure 6
Structure 7
Structure 8

See also[edit]

References[edit]

  1. ^ James M. Mathews, Amy S. Etheridge and Sherry R. Black. "Inhibition of Human Cytochrome P450 Activities by Kava Extract and Kavalactones". 
  2. ^ Dr Joji Malani (2002). "Evaluation of the effects of Kava on the Liver" (PDF). Retrieved 2008-01-05. 
  3. ^ AC Brown (2007). "Traditional kava beverage consumption and liver function tests in a predominantly Tongan population in Hawaii revealed no liver impairment.". Retrieved 2009-03-17. 
  4. ^ Tang, J; Dunlop, RA; Rowe, A; Rodgers, KJ; Ramzan, I (2010). "Kavalactones Yangonin and Methysticin Induce Apoptosis in Human Hepatocytes (HepG2) In Vitro.". Phytotherapy research : PTR 25 (3): n/a. doi:10.1002/ptr.3283. PMID 20734326. 
  5. ^ Zi X, Simoneau AR (April 2005). "Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice.". Cancer Research 65 (8): 3479–86. doi:10.1158/0008-5472.CAN-04-3803. PMID 15833884. 
  6. ^ Ramez N. Eskander1, Leslie M. Randall1, Toshinori Sakai, Yi Guy, Bang Hoang, Xiaolin Zi. "Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line". 
  7. ^ Naumov, P.; Dragull, K.; Yoshioka, M.; Tang, C.-S.; Ng, S. W. (2008). "Structural Characterization of Genuine (-)-Pipermethystine, (-)-Epoxypipermethystine, (+)-Dihydromethysticin and Yangonin from the Kava Plant (Piper methysticum)". Natural Product Communications 3 (8): 1333–1336. 
  8. ^ Shulgin, A. (1973). "The narcotic pepper - the chemistry and pharmacology of Piper methysticum and related species". Bulletin on Narcotics (UNODC) (2): 59–74. 

External links[edit]