Kavalactone
Kavalactones are a class of lactone compounds found in kava roots and Alpinia zerumbet (shell ginger)[1] and in several Gymnopilus, Phellinus and Inonotus fungi.[2] Some kavalactones are bioactive. They are responsible for the psychoactive, analgesic, euphoric and sedative effects of kava.[3][4]
Bioactivity
Kava extract interacts with many pharmaceuticals and herbal medications. In human volunteers, in vivo inhibition includes CYP1A2[5] and CYP2E1[6] through use of probe drugs to measure inhibition.
Research
Its anxiolytic and hepatotoxic properties have been investigated.[7][8][9]
The major kavalactones (except for [[desmethoxyyangonin|desTemplate:ShymethoxyTemplate:Shyyangonin]]) potentiate GABAA receptors, which may underlie the anxiolytic and sedative properties of kava. Further, inhibition of the reuptake of [[norepinephrine|norTemplate:ShyepiTemplate:ShynephTemplate:Shyrine]] and dopamine, binding to the CB1 receptor,[10] inhibition of voltage-gated sodium and calcium channels, and monoamine oxidase B reversible inhibition are additional pharmacological actions that have been reported for kavalactones.[11]
Toxicity
Several kavalactones (e.g., methysticin and yangonin) affect a group of enzymes involved in metabolism, called the CYP450 system. Hepatotoxicity occurred in a small portion of previously healthy kava users,[8][12] particularly from extracts, as opposed to whole root powders.
Compounds
Script error: No such module "Labelled list hatnote". At least 18 different kavalactones are known,[1] with methysticin being the first identified.[13] Multiple analogues, such as ethysticin, have also been isolated.[14] Some consist of a substituted α-pyrone as the lactone, while others are partially saturated.
The average elimination half-life of kavalactones typically present in kava root is 9 hr.[15]
| 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 | |
Biosynthesis
The kavalactone biosynthetic pathway in Piper methysticum was described in 2019.[16]
See also
References
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External links
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- The great kava boom: how Fiji's beloved psychoactive brew is going global The Guardian, 2020