Kavalactones are a class of lactone compounds found in kava roots and Alpinia zerumbet (shell ginger).[1] Some kavalactones are bioactive.[2][3]
Kava extract interacts with many pharmaceuticals and herbal medications. In human volunteers, in vivo inhibition includes CYP1A2[4] and CYP2E1[5] through use of probe drugs to measure inhibition.
Its anxiolytic and hepatotoxicity activities have been investigated.[6][7][8]
The major kavalactones (except for desmethoxyyangonin) potentiate GABAA receptors, which may underlie the anxiolytic and sedative properties of kava. Further, inhibition of the reuptake of norepinephrine and dopamine, binding to the CB1 receptor,[9] inhibition of voltage-gated sodium and calcium channels, and monoamine oxidase B reversible inhibition are additional pharmacological actions that have been reported for kavalactones.[10]
Kavalactone-type compounds may help protect against high glucose induced cell damage.[2]
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,[7][11] particularly from extracts, as opposed to whole root powders.
At least 18 different kavalactones are known,[1] with methysticin being the first identified.[12] Multiple analogues, such as ethysticin, have also been isolated.[13] 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.[14]
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 |
The kavalactone biosynthetic pathway in Piper methysticum was described in 2019.[15]