Dihydrokavain
Chemical compound
From Wikipedia, the free encyclopedia
Dihydrokavain is one of the six major kavalactones found in the kava plant.[1] It showed the highest systemic exposure among all six major kavalactones tested, indicating it may play a central role in kava's pharmacological effects in humans. The anxiolytic effects of kava are primarily attributed to dihydrokavain.
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| IUPAC name
4-Methoxy-6-(2-phenylethyl)-5,6-dihydro-2H-pyran-2-one | |
| Other names
Dihydrokawain Marindinin | |
| Identifiers | |
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CompTox Dashboard (EPA) |
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| Properties | |
| C14H16O3 | |
| Molar mass | 232.27 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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.[2] Dihydrokavain showed the highest systemic exposure among all six major kavalactones tested, indicating it may play a central role in kava's pharmacological effects in humans.[3] Additionally, intraperitoneal administration of dihydrokavain (150 mg/kg) in mice produced a significant analgesic effect.[4]
Among the six major kavalactones, it showed the strongest inhibition of norepinephrine-induced calcium signaling in lung cancer cells by antagonizing β-adrenergic receptors, suggesting its potential role in kava's anxiolytic and cancer-preventive effects.[5]
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.[6] 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.[7]
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.[8]
Dihydrokavain bears some structural similarity to the strobilurins and has some fungicidal activity.[9]
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.[10]