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{{Short description|Group of chemical compounds}} |
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[[Image:Kavalactone-general-numbered.svg|300px|thumb|right|The general structure of the kavalactones, without the R<sub>1</sub>-R<sub>2</sub> -O-CH<sub>2</sub>-O- bridge and with all possible C=C double bonds shown.]] |
[[Image:Kavalactone-general-numbered.svg|300px|thumb|right|The general structure of the kavalactones, without the R<sub>1</sub>-R<sub>2</sub> -O-CH<sub>2</sub>-O- bridge and with all possible C=C double bonds shown.]] |
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'''Kavalactones''' are a class of [[lactone]] compounds found in [[kava]] roots and ''[[Alpinia zerumbet]]'' (shell ginger).<ref name=Syn>{{cite journal |doi=10.1055/s-0040-1706044 |title=A Review on Synthetic Approaches towards Kavalactones |date=2021 |last1=Tadiparthi |first1=Krishnaji |last2=Anand |first2=Pragya |journal=Synthesis |volume=53 |issue=19 |pages=3469–3484 |s2cid=236392304 }}</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">{{Cite journal | url=https://www.tandfonline.com/doi/abs/10.1080/14786419.2021.2023866?journalCode=gnpl20 | doi=10.1080/14786419.2021.2023866 | title=Kavalactones isolated from Alpinia zerumbet (Pers.) Burtt. Et Smith with protective effects against human umbilical vein endothelial cell damage induced by high glucose | year=2022 | last1=You | first1=Hualin | last2=He | first2=Min | last3=Pan | first3=Di | last4=Fang | first4=Guanqin | last5=Chen | first5=Yan | last6=Zhang | first6=Xu | last7=Shen | first7=Xiangchun | last8=Zhang | first8=Nenling | journal=Natural Product Research | volume=36 | issue=22 | pages=5740–5746 | pmid=34989299 | s2cid=245771677 }}</ref><ref>{{cite journal|title=Inhibition of Human Cytochrome P450 Activities by Kava Extract and Kavalactones|journal=Drug Metabolism and Disposition |volume=30 |issue=11 |pages=1153–1157 |author1=James M. Mathews |author2=Amy S. Etheridge |author3=Sherry R. Black |url=http://dmd.aspetjournals.org/content/30/11/1153.short|doi=10.1124/dmd.30.11.1153 |year=2002 |pmid=12386118 }}</ref> |
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'''Kavalactones''' are a class of [[lactone]] compounds found in the [[kava]] shrub. Kavalactones are under research for potential to have various [[psychotropic drug|psychotropic]] effects, including [[anxiolytic]] and [[sedative]]/[[hypnotic]] activities. |
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==Bioactivity== |
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==Enzyme inhibition== |
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Kava extract interacts with many pharmaceuticals and herbal medications. In human volunteers, in vivo inhibition includes CYP1A2<ref>{{Cite journal |last1=Russmann |first1=S |last2=Lauterburg |first2=B |last3=Barguil |first3=Y |last4=Choblet |first4=E |last5=Cabalion |first5=P |last6=Rentsch |first6=K |last7=Wenk |first7=M |date=2005 |title=Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens? |url=http://doi.wiley.com/10.1016/j.clpt.2005.01.021 |journal=[[Clinical Pharmacology & Therapeutics]] |language=en |volume=77 |issue=5 |pages=453–454 |doi=10.1016/j.clpt.2005.01.021|pmid=15900292 |s2cid=36009940 }}</ref> and CYP2E1<ref>{{Cite journal |last1=Gurley |first1=B |last2=Gardner |first2=S |last3=Hubbard |first3=M |last4=Williams |first4=D |last5=Gentry |first5=W |last6=Khan |first6=I |last7=Shah |first7=A |date=2005 |title=In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes |journal=[[Clinical Pharmacology & Therapeutics]] |language=en |volume=77 |issue=5 |pages=415–426 |doi=10.1016/j.clpt.2005.01.009 |pmc=1894911 |pmid=15900287}}</ref> through use of probe drugs to measure inhibition. |
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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.<ref>{{cite journal|title=Inhibition of Human Cytochrome P450 Activities by Kava Extract and Kavalactones|journal=Drug Metabolism and Disposition |volume=30 |issue=11 |pages=1153–1157 |author1=James M. Mathews |author2=Amy S. Etheridge |author3=Sherry R. Black |url=http://dmd.aspetjournals.org/content/30/11/1153.short|doi=10.1124/dmd.30.11.1153 |year=2002 |pmid=12386118 }}</ref> |
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== Research == |
== Research == |
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Its [[anxiolytic]] and [[hepatotoxicity]] activities have been investigated.<ref name=":0">{{Cite journal|last1=Sarris|first1=Jerome|last2=LaPorte|first2=Emma|last3=Schweitzer|first3=Isaac|date=2011-01-01|title=Kava: A Comprehensive Review of Efficacy, Safety, and Psychopharmacology|journal=Australian & New Zealand Journal of Psychiatry|language=en|volume=45|issue=1|pages=27–35|doi=10.3109/00048674.2010.522554|pmid=21073405|s2cid=42935399}}</ref><ref name="teschke">{{cite journal|pmid=21756963|year=2011|last1=Teschke|first1=R|title=Proposal for a kava quality standardization code|journal=Food and Chemical Toxicology|volume=49|issue=10|pages=2503–16|last2=Lebot|first2=V|doi=10.1016/j.fct.2011.06.075}}</ref><ref>{{cite journal|pmc=4325077|year=2013|last1=Wang|first1=J|title=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=Journal of Food Science and Technology|volume=52|issue=2|pages=1164–1169|last2=Qu|first2=W|last3=Bittenbender|first3=H. C.|last4=Li|first4=Q. X.|doi=10.1007/s13197-013-1047-2|pmid=25694734}}</ref> |
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The major kavalactones (except for [[desmethoxyyangonin]]) potentiate [[GABAA receptor|GABA<sub>A</sub> receptors]], which may underlie the anxiolytic and sedative properties of kava. Further, [[Reuptake inhibitor|inhibition]] of the [[reuptake]] of [[norepinephrine]] and [[dopamine]], binding to the [[CB1 receptor|CB<sub>1</sub> receptor]],<ref name="pmid22525682">{{cite journal | vauthors = Ligresti A, Villano R, Allarà M, Ujváry I, Di Marzo V | title = Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB₁ receptor ligand | journal = Pharmacol. Res. | volume = 66 | issue = 2 | pages = 163–9 | year = 2012 | pmid = 22525682 | doi = 10.1016/j.phrs.2012.04.003 }}</ref> inhibition of voltage-gated [[sodium channel|sodium]] and [[voltage-gated calcium channel|calcium channels]], and [[monoamine oxidase B]] reversible inhibition are additional pharmacological actions that have been reported for kavalactones.<ref name="pmid12383029">{{cite journal | vauthors = Singh YN, Singh NN | title = Therapeutic potential of kava in the treatment of anxiety disorders | journal = CNS Drugs | volume = 16 | issue = 11 | pages = 731–43 | year = 2002 | pmid = 12383029 | doi = 10.2165/00023210-200216110-00002| s2cid = 34322458 }}</ref> |
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| ⚫ | Several kavalactones (e.g.[[methysticin]] and [[yangonin]]) |
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Kavalactone-type compounds may help protect against high glucose induced cell damage.<ref name="tandfonline.com"/> |
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Numerous kavalactones have [[apoptosis|apoptotic]] effects on various human tissues, a mechanism under preliminary study for the toxic effects of kava use.<ref>{{cite journal | last1 = Tang | first1 = J | last2 = Dunlop | first2 = RA | last3 = Rowe | first3 = A | last4 = Rodgers | first4 = KJ | last5 = Ramzan | first5 = I | title = Kavalactones Yangonin and Methysticin Induce Apoptosis in Human Hepatocytes (HepG2) In Vitro. | journal = Phytotherapy Research | pages = 417–23| year = 2010 | pmid = 20734326 | doi = 10.1002/ptr.3283 | volume = 25 | issue = 3| s2cid = 19717477 }}</ref> |
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Toxic reactions are appear to be idiosyncratic and necrotic by nature. Concurrent consumption of another hepatotoxic substance, such as [[alcohol (drug)|alcohol]] or [[paracetamol]], may significantly increase the risk.{{mcn|date=August 2020}} |
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| ⚫ | Several kavalactones (e.g., [[methysticin]] and [[yangonin]]) affect a group of [[enzyme]]s involved in [[metabolism]], called the [[Cytochrome P450|CYP450 system]]. [[Hepatotoxicity]] occurred in a small portion of previously healthy kava users,<ref name=teschke/><ref name="teschke2">{{cite journal|pmid=21442674|year=2011|last1=Teschke|first1=R|title=Kava and kava hepatotoxicity: Requirements for novel experimental, ethnobotanical and clinical studies based on a review of the evidence|journal=Phytotherapy Research|volume=25|issue=9|pages=1263–74|last2=Qiu|first2=S. X.|last3=Xuan|first3=T. D.|last4=Lebot|first4=V|doi=10.1002/ptr.3464|s2cid=19142750}}</ref> particularly from extracts, as opposed to whole root powders. |
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== Compounds == |
== Compounds == |
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{{see also|Flavokavain}} |
{{see also|Flavokavain}} |
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At least 18 different kavalactones |
At least 18 different kavalactones are known,<ref name=Syn/> with methysticin being the first identified.<ref> |
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{{ cite journal |
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| doi = 10.1177/1934578X0800300819 |
| doi = 10.1177/1934578X0800300819 |
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| s2cid = 92030132 |
| s2cid = 92030132 |
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</ref> |
</ref> |
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| url = http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1973-01-01_2_page008.html |
| url = http://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1973-01-01_2_page008.html |
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}}</ref> |
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Some consist of a substituted [[α-pyrone]] as the lactone while others are partially saturated. |
Some consist of a substituted [[α-pyrone]] as the lactone, while others are partially saturated. |
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The average [[elimination half-life]] of kavalactones typically present in kava root is 9 hr.<ref>{{cite web|url=http://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/piper-methysticum.html|title=Kava (''Piper methysticum''): Pharmacodynamics/Kinetics|publisher=Sigma-Aldrich Co. LLC|date=2010}}</ref> |
The average [[elimination half-life]] of kavalactones typically present in kava root is 9 hr.<ref>{{cite web|url=http://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/piper-methysticum.html|title=Kava (''Piper methysticum''): Pharmacodynamics/Kinetics|publisher=Sigma-Aldrich Co. LLC|date=2010}}</ref> |
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==Biosynthesis== |
==Biosynthesis== |
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The kavalactone biosynthetic pathway in |
The kavalactone biosynthetic pathway in ''Piper methysticum'' was described in 2019.<ref name="Pluskal Torrens-Spence Fallon De Abreu pp. 867–878">{{cite journal | last1=Pluskal | first1=Tomáš | last2=Torrens-Spence | first2=Michael P. | last3=Fallon | first3=Timothy R. | last4=De Abreu | first4=Andrea | last5=Shi | first5=Cindy H. | last6=Weng | first6=Jing-Ke | title=The biosynthetic origin of psychoactive kavalactones in kava | journal=Nature Plants | publisher=Springer Science and Business Media LLC | volume=5 | issue=8 | date=2019-07-22 | issn=2055-0278 | doi=10.1038/s41477-019-0474-0 | pages=867–878| pmid=31332312 | hdl=1721.1/124692 | s2cid=198139136 | hdl-access=free }}</ref> |
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==See also== |
==See also== |
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Latest revision as of 03:47, 7 January 2025
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
[edit]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
[edit]Its anxiolytic and hepatotoxicity activities have been investigated.[7][8][9]
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,[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]
Kavalactone-type compounds may help protect against high glucose induced cell damage.[3]
Toxicity
[edit]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
[edit]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 | |
 |
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 |
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Biosynthesis
[edit]The kavalactone biosynthetic pathway in Piper methysticum was described in 2019.[16]
See also
[edit]References
[edit]- ^ 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.
- ^ https://jpharmsci.org/article/S0022-3549(15)37017-9/abstract
- ^ 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 34989299. S2CID 245771677.
- ^ 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.