Dihydrokavain

{{chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 450846926

| Name = Dihydrokavain

| ImageFile = Dihydrokavain.svg

| ImageSize = 150

| ImageName = Chemical structure of dihydrokavain

| ImageAlt = Chemical structure of dihydrokavain

| ImageFile2 = Dihydrokavain 3D BS.png

| ImageSize2 = 150

| ImageName2 = An accurate three dimensional representation of the molecule of Dihydrokavain in ball-and-stick format

| ImageAlt2 = An accurate three dimensional representation of the molecule of Dihydrokavain in ball-and-stick forma

| IUPACName = 4-Methoxy-6-(2-phenylethyl)-5,6-dihydro-2H-pyran-2-one

| OtherNames = Dihydrokawain
Marindinin

|Section1={{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 587-63-3

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = NW8ZGW9XRZ

| PubChem = 98356

| SMILES = COC1=CC(=O)OC(C1)CCC2=CC=CC=C2

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 88817

| InChI = 1/C14H16O3/c1-16-13-9-12(17-14(15)10-13)8-7-11-5-3-2-4-6-11/h2-6,10,12H,7-9H2,1H3

| InChIKey = VOOYTQRREPYRIW-UHFFFAOYAX

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C14H16O3/c1-16-13-9-12(17-14(15)10-13)8-7-11-5-3-2-4-6-11/h2-6,10,12H,7-9H2,1H3

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = VOOYTQRREPYRIW-UHFFFAOYSA-N

| MeSHName =

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|Section2={{Chembox Properties

| Formula = C₁₄H₁₆O₃

| MolarMass = 232.27 g/mol

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Dihydrokavain is one of the six major kavalactones found in the kava plant.{{cite journal|title=Evaluation of the effects of Kava on the Liver|journal=Fiji School of Medicine|date=2002-12-03|first=Joji|last=Malani|url=http://www.spc.int/cis/documents/Kava%20article%20DrMalani.pdf|accessdate=2009-09-04|archive-url=https://web.archive.org/web/20090320001735/http://www.spc.int/cis/documents/Kava%20article%20DrMalani.pdf|archive-date=2009-03-20|url-status=dead}}

The anxiolytic effects of kava are primarily attributed to dihydrokavain. In animal models, such as socially isolated chicks, dihydrokavain reduces anxiety-related distress without causing the sedation typically seen with standard anxiolytic drugs. Beyond its anxiolytic properties, dihydrokavain has demonstrated anti-inflammatory and analgesic effects, including inhibition of cyclooxygenase (COX) enzymes and suppression of tumor necrosis factor alpha (TNFα). It also shows potential anti-diabetic activity by activating AMP-activated protein kinase (AMPK) signaling and improving glycemic control in Drosophila models. Additionally, dihydrokavain inhibits several cytochrome P450 enzymes, indicating a potential for drug interactions, and shares structural similarities with strobilurins, contributing to mild fungicidal activity.

Pharmacology

Kava extract reduces anxiety-related distress in chicks mainly due to its dihydrokavain content, which provides anxiolytic effects without the sedation caused by standard drugs like chlordiazepoxide.{{cite journal|last=Feltenstein|first=MW|author2=LC Lambdin |author3=M Ganzera |author4=H Ranjith |author5=W Dharmaratne |author6=NP Nanayakkara |author7=IA Khan |author8=KJ Sufka |title=Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedure.|journal=Phytotherapy Research|date=March 2003|volume=17|issue=3|pages=210–216|doi=10.1002/ptr.1107|pmid=12672148|s2cid=10548965}}

Dihydrokavain bears some structural similarity to the strobilurins and has some fungicidal activity.{{cite journal | last1=Zakharychev | first1=Vladimir V | last2=Kovalenko | first2=Leonid V | title=Natural compounds of the strobilurin series and their synthetic analogues as cell respiration inhibitors | journal=Russian Chemical Reviews | volume=67 | issue=6 | date=1998-06-30 | issn=0036-021X | doi=10.1070/rc1998v067n06abeh000426 | pages=535–544 | bibcode=1998RuCRv..67..535Z | s2cid=95676421}}

An analogue of the molecule, 56DHK, is a compound in Alpinia mutica and improves hyperglycemia in a diabetic Drosophila model by activating AMP-activated protein kinase (AMPK) signaling and modulating related metabolic genes, showing potential as a novel anti-diabetic agent.{{Cite journal |last1=Hadiza Muhammad Maiturare |last2=Mudassir Aliyu Magaji |last3=Muhammad Kabiru Dallatu |last4=Kabir Magaji Hamid |last5=Mustapha Umar Imam |last6=Ibrahim Malami |date=2022 |title=5,6-dehydrokawain improves glycaemic control by modulating AMPK target genes in Drosophila with a high-sucrose diet-induced hyperglycaemia |url=https://pubag.nal.usda.gov/catalog/7719064 |journal=Phytomedicine Plus |language=English |volume=2 |issue=2 |pages=100261– |doi=10.1016/j.phyplu.2022.100261 |s2cid=247649601 |issn=2667-0313|doi-access=free }}

Dihydrokavain has been shown to inhibit cyclooxygenase enzymes, reducing COX-1 activity by approximately 58% and COX-2 by 28%, suggesting potential anti-inflammatory effects.Rowe A, Smith JV, Booth GM. Kavalactone pharmacophores for major cellular drug targets. Mini Reviews in Medicinal Chemistry. 2011;11(1):79–83. PMID: 21222507. It also reduces TNFα secretion in lipopolysaccharide-stimulated THP-1 cells (a human acute monocytic leukemia-derived cell line) at a concentration of 50 μg/mL.Bian T, Zhang M, Zhang S, Xu L. Kava as a Clinical Nutrient: Promises and Challenges. Nutrients. 2020;12(10):3044. doi:10.3390/nu12103044. PMID: 33036563.

In vitro studies show that dihydrokavain inhibits the cytochrome P450 enzymes CYP2C9 (IC₅₀ = 130.95 μM), CYP2C19 (IC₅₀ = 10.05 μM), and CYP3A4 (IC₅₀ = 78.59 μM), indicating potential drug interaction risks.Anke J, Ramzan I. Pharmacokinetic and pharmacodynamic drug interactions with kava (Piper methysticum Forst. f.). Journal of Ethnopharmacology. 2004;93(2–3):153–60. doi:10.1016/j.jep.2004.03.054. PMID: 15172113.

Additionally, intraperitoneal administration of dihydrokavain (150 mg/kg) in mice produced a significant analgesic effect.Jamieson DD, Duffield PH. The antinociceptive actions of kava components in mice. Clinical and Experimental Pharmacology and Physiology. 1990;17(7):495–507. doi:10.1111/j.1440-1681.1990.tb01452.x. PMID: 2226874.

References

Category:Kavalactones

Category:Anxiolytics

Category:GABAA receptor positive allosteric modulators

Category:Monoamine oxidase inhibitors