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Group of chemical compounds
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).
[1] Some kavalactones are bioactive.
[2]
[3]
Bioactivity
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.
Research
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]
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,
[7]
[11] particularly from extracts, as opposed to whole root powders.
Compounds
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]
Kavalactones: General structures
Structure 1
Structure 2
Structure 3
Structure 4
Structure 5
Structure 6
Structure 7
Structure 8
Biosynthesis
The kavalactone biosynthetic pathway in Piper methysticum was described in 2019.
[15]
See also
References
^
a
b Tadiparthi, Krishnaji; Anand, Pragya (2021). "A Review on Synthetic Approaches towards Kavalactones". Synthesis . 53 (19): 3469–3484.
doi :
10.1055/s-0040-1706044 .
S2CID
236392304 .
^
a
b You, Hualin; He, Min; Pan, Di; Fang, Guanqin; Chen, Yan; Zhang, Xu; Shen, Xiangchun; Zhang, Nenling (2022).
"Kavalactones isolated from Alpinia zerumbet (Pers.) Burtt. Et Smith with protective effects against human umbilical vein endothelial cell damage induced by high glucose" . Natural Product Research . 36 (22): 5740–5746.
doi :
10.1080/14786419.2021.2023866 .
PMID
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^ James M. Mathews; Amy S. Etheridge; Sherry R. Black (2002).
"Inhibition of Human Cytochrome P450 Activities by Kava Extract and Kavalactones" . Drug Metabolism and Disposition . 30 (11): 1153–1157.
doi :
10.1124/dmd.30.11.1153 .
PMID
12386118 .
^ Russmann, S; Lauterburg, B; Barguil, Y; Choblet, E; Cabalion, P; Rentsch, K; Wenk, M (2005).
"Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens?" .
Clinical Pharmacology & Therapeutics . 77 (5): 453–454.
doi :
10.1016/j.clpt.2005.01.021 .
PMID
15900292 .
S2CID
36009940 .
^ Gurley, B; Gardner, S; Hubbard, M; Williams, D; Gentry, W; Khan, I; Shah, A (2005).
"In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes" .
Clinical Pharmacology & Therapeutics . 77 (5): 415–426.
doi :
10.1016/j.clpt.2005.01.009 .
PMC
1894911 .
PMID
15900287 .
^ Sarris, Jerome; LaPorte, Emma; Schweitzer, Isaac (2011-01-01). "Kava: A Comprehensive Review of Efficacy, Safety, and Psychopharmacology". Australian & New Zealand Journal of Psychiatry . 45 (1): 27–35.
doi :
10.3109/00048674.2010.522554 .
PMID
21073405 .
S2CID
42935399 .
^
a
b Teschke, R; Lebot, V (2011). "Proposal for a kava quality standardization code". Food and Chemical Toxicology . 49 (10): 2503–16.
doi :
10.1016/j.fct.2011.06.075 .
PMID
21756963 .
^ Wang, J; Qu, W; Bittenbender, H. C.; Li, Q. X. (2013).
"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" . Journal of Food Science and Technology . 52 (2): 1164–1169.
doi :
10.1007/s13197-013-1047-2 .
PMC
4325077 .
PMID
25694734 .
^ Ligresti A, Villano R, Allarà M, Ujváry I, Di Marzo V (2012). "Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB₁ receptor ligand". Pharmacol. Res . 66 (2): 163–9.
doi :
10.1016/j.phrs.2012.04.003 .
PMID
22525682 .
^ Singh YN, Singh NN (2002). "Therapeutic potential of kava in the treatment of anxiety disorders". CNS Drugs . 16 (11): 731–43.
doi :
10.2165/00023210-200216110-00002 .
PMID
12383029 .
S2CID
34322458 .
^ Teschke, R; Qiu, S. X.; Xuan, T. D.; Lebot, V (2011). "Kava and kava hepatotoxicity: Requirements for novel experimental, ethnobotanical and clinical studies based on a review of the evidence". Phytotherapy Research . 25 (9): 1263–74.
doi :
10.1002/ptr.3464 .
PMID
21442674 .
S2CID
19142750 .
^
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.
doi :
10.1177/1934578X0800300819 .
S2CID
92030132 .
^
Shulgin, A. (1973).
"The narcotic pepper - the chemistry and pharmacology of Piper methysticum and related species" . Bulletin on Narcotics (2): 59–74.
^
"Kava (Piper methysticum ): Pharmacodynamics/Kinetics" . Sigma-Aldrich Co. LLC. 2010.
^ Pluskal, Tomáš; Torrens-Spence, Michael P.; Fallon, Timothy R.; De Abreu, Andrea; Shi, Cindy H.; Weng, Jing-Ke (2019-07-22). "The biosynthetic origin of psychoactive kavalactones in kava". Nature Plants . 5 (8). Springer Science and Business Media LLC: 867–878.
doi :
10.1038/s41477-019-0474-0 .
hdl :
1721.1/124692 .
ISSN
2055-0278 .
PMID
31332312 .
S2CID
198139136 .
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