Kavalactone

File:Kavalactone-general-numbered.svg

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 kava roots and Alpinia zerumbet (shell ginger)<ref name=Syn>Template:Cite journal</ref> and in several Gymnopilus, Phellinus and Inonotus fungi.<ref>https://jpharmsci.org/article/S0022-3549(15)37017-9/abstract</ref> Some kavalactones are bioactive. They are responsible for the psychoactive, analgesic, euphoric and sedative effects of kava.<ref name="tandfonline.com">Template:Cite journal</ref><ref>Template:Cite journal</ref>

Bioactivity

Kava extract interacts with many pharmaceuticals and herbal medications. In human volunteers, in vivo inhibition includes CYP1A2<ref>Template:Cite journal</ref> and CYP2E1<ref>Template:Cite journal</ref> through use of probe drugs to measure inhibition.

Research

Its anxiolytic and hepatotoxic properties have been investigated.<ref name=":0">Template:Cite journal</ref><ref name="teschke">Template:Cite journal</ref><ref>Template:Cite journal</ref>

The major kavalactones (except for [[desmethoxyyangonin|desTemplate:ShymethoxyTemplate:Shyyangonin]]) potentiate GABA_A 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,<ref name="pmid22525682">Template:Cite journal</ref> inhibition of voltage-gated sodium and calcium channels, and monoamine oxidase B reversible inhibition are additional pharmacological actions that have been reported for kavalactones.<ref name="pmid12383029">Template:Cite journal</ref>

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,<ref name=teschke/><ref name="teschke2">Template:Cite journal</ref> particularly from extracts, as opposed to whole root powders.

Compounds

Template:See also At least 18 different kavalactones are known,<ref name=Syn/> with methysticin being the first identified.<ref> Template:Cite journal </ref> Multiple analogues, such as ethysticin, have also been isolated.<ref> Template:Cite journal</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name="Pluskal Torrens-Spence Fallon De Abreu pp. 867–878">Template:Cite journal</ref>

See also

• Pipermethystine

External links

• {{#invoke:citation/CS1|citation

|CitationClass=web }}

• The great kava boom: how Fiji's beloved psychoactive brew is going global The Guardian, 2020