Desmethoxyyangonin

Desmethoxyyangonin at a Glance

Desmethoxyyangonin (DMY) is one of the six major kavalactones — the styryl-pyrone constituents that carry most of the psychoactivity of kava (Piper methysticum). Structurally it is the des-methoxy analogue of its close relative yangonin: the same styrylpyrone skeleton, minus one aromatic methoxy group.

What makes DMY worth its own page is that it does not behave like the calming, GABAergic kavalactones. Among the six, DMY is the most potent reversible inhibitor of monoamine oxidase B (MAO-B) ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}, and in rats it raises dopamine in the nucleus accumbens — the mesolimbic reward pathway ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}. That monoaminergic, faintly mood-elevating signature is the proposed molecular basis for the mild euphoria and lift many kava drinkers describe, and it sits in deliberate contrast to kavain, whose anxiolysis runs through GABA-A potentiation ^{3Reference 3Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}.

DMY itself is not the constituent responsible for kava’s rare hepatotoxicity — that concern tracks the chalcone flavokavains and the aerial-part alkaloid pipermethystine, not the root kavalactones ^{10,11,12Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →Reference 11Teschke R et al. · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}. Its own cautions are pharmacological: MAO-B inhibition, additive CNS sedation, and the kavalactone class’s cytochrome-P450 interactions.

The MAO-B / Dopaminergic Signature

This is the section only DMY needs — the reason it is not interchangeable with the other kavalactones.

Reversible MAO-B inhibition. When the pure synthetic kava pyrones were tested against human platelet MAO-B, they inhibited the enzyme in a rank order, and desmethoxyyangonin was the most potent of the six ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}. The kava extract itself was a reversible inhibitor (IC50 24 µM in intact platelets, 1.2 µM in disrupted homogenates), and DMY showed a competitive inhibition pattern with a mean Ki of 0.28 µM — an order of magnitude more potent than methysticin, the next in line, and far ahead of kavain ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}. Reversibility matters: unlike an irreversible MAO inhibitor drug, a reversible inhibitor’s effect fades as the compound clears, which lowers (without eliminating) the interaction and tyramine concerns.

Raising dopamine in the reward pathway. In an in-vivo microdialysis study of the rat mesolimbic system, the individual kavalactones diverged sharply. Desmethoxyyangonin increased dopamine levels in the nucleus accumbens; yangonin drove dopamine below the detection limit; and kavain lowered it at low doses, while dihydrokavain, methysticin and dihydromethysticin produced no significant dopamine change ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}. The authors read the accumbens dopamine rise as a plausible substrate for kava’s “relaxing and slightly euphoric” actions ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}.

Put together, MAO-B inhibition (which slows the breakdown of dopamine and other monoamines) and a direct rise in accumbens dopamine point the same way: DMY is the monoaminergic, “up” side of the kava profile, distinct from the sedative-anxiolytic kavalactones.

Desmethoxyyangonin vs. Kavain

The two most-studied kavalactones pull in different pharmacological directions, and holding them apart is the key to understanding kava’s mixed “calm-but-lifted” quality.

• Kavain — the principal anxiolytic. A positive allosteric modulator of GABA-A receptors ^{3Reference 3Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →} and a blocker of voltage-gated sodium channels ^{4Reference 4Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na⁺-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →}, it drives the sedative, tension-easing side of kava.
• Desmethoxyyangonin — the monoaminergic counterpoint. The most potent kavalactone MAO-B inhibitor ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →} and the one that raises accumbens dopamine ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}, contributing the mild mood-elevating lift rather than sedation.

Neither acts alone: kava is consumed as a mixture of all six, and its net effect is the sum of a GABAergic calming component and a monoaminergic activating one. DMY is the clearest single-molecule handle on the second.

What It's Used For

DMY’s evidence is narrow but distinctive. The two load-bearing findings are isolate studies — pure synthetic pyrones on platelet enzyme ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →} and single kavalactones by microdialysis in rats ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →} — while kava’s actual clinical evidence (anxiety) belongs to the whole standardised extract, not to DMY ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. DMY’s scores are modest by design: the isolate data are in-vitro/animal, and the human anxiolytic data are the whole extract, not this molecule.

01MAO-B Inhibition (Monoaminergic Tone)Shaky40%Pure-pyrone assay on human platelet MAO-B; DMY most potent, competitive, Ki 0.28 µM (isolate, in vitro) ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}

02Dopaminergic Mood ElevationShaky34%Rat nucleus-accumbens microdialysis: DMY raises dopamine (isolate, animal) ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}

03Anxiolysis (Kavalactone Complex)Shaky30%Human GAD RCT of whole kava extract — the plant, not the isolated molecule ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}

Mechanisms

The load-bearing rows are the top two: MAO-B inhibition plus an accumbens dopamine rise are the same monoaminergic story from two angles, and together they distinguish DMY from the GABAergic anxiolytic kavalactones.

Pharmacokinetics

Kavalactones as a class are small, lipophilic styryl-pyrones that are well absorbed orally and cross the blood–brain barrier, which is why kava is centrally active by mouth. Compound-specific human pharmacokinetics for desmethoxyyangonin are not established — there are no published human C­max, half-life or oral-bioavailability figures for the isolate, and the free-DMY concentration reaching brain MAO-B after ordinary kava intake is unknown, which is the key caveat on translating the in-vitro potency ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}. What is documented at the class level is that kavalactones inhibit several cytochrome-P450 enzymes, the mechanistic basis of kava’s herb–drug interaction potential ^{7,9Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →Reference 9Bian T et al. · 2020Kava as a clinical nutrient: promises and challengesView study →}. Preparation matters: measured kavalactone content (including DMY) varies enormously between products, and label claims can differ from assay by large margins ^{7Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →}.

Clinical Trials

There are no clinical trials of isolated desmethoxyyangonin. Human evidence exists only for whole kava: the standardised aqueous extract has been tested in generalized anxiety disorder ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}, within which DMY is one minor constituent of the kavalactone mixture.

Last checked: July 2026.

Isolate vs. Plant Studies

DMY’s evidence base splits cleanly. The mechanistic findings are the isolate: pure synthetic desmethoxyyangonin tested on human platelet MAO-B ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →} and single-kavalactone microdialysis in rats ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →} — a real strength for attributing the monoaminergic action to this molecule rather than the mixture. The clinical evidence, by contrast, is entirely the plant: kava’s anxiety RCTs use the standardised whole extract ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}, where DMY is a minor fraction and the anxiolysis is usually credited to other kavalactones ^{3,4Reference 3Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →Reference 4Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na⁺-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →}. So the correct framing is: strong isolate mechanism, no isolate clinical data, and a human anxiolytic signal that belongs to whole kava, not to DMY alone.

Its Role in Plants

Desmethoxyyangonin is a styrylpyrone, a class built from the phenylpropanoid (hydroxycinnamic-acid) pathway. Reconstruction of the recently discovered kava styrylpyrone biosynthetic pathway in engineered yeast produced DMY and yangonin — the two 7,8-unsaturated styrylpyrones — alongside their 7,8-saturated relatives, confirming that DMY sits on the same enzymatic route from hydroxycinnamic-acid precursors that the plant uses, via a styrylpyrone synthase with broad substrate tolerance ^{13Reference 13Wu Y et al. · 2022De novo biosynthesis of diverse plant-derived styrylpyrones in Saccharomyces cerevisiaeView study →}. In the plant these styryl-pyrones are secondary metabolites concentrated in the root and rhizome; their ecological role (defence versus signalling) is less well defined than their pharmacology, and is a plant-biology function that should not be read as human activity.

Prevalence in Nature

Desmethoxyyangonin is, for practical purposes, a kava-specific molecule: it is one of the six major kavalactones of Piper methysticum root and rhizome, and only trace/minor styrylpyrone occurrences are reported elsewhere in the genus. Within kava it is a minor-to-moderate share of the kavalactone fraction, and that share is not fixed — total and relative kavalactone content vary widely with cultivar/chemotype (noble vs. tudei/wichmannii), plant part (peeled root vs. rhizome vs. aerial tissue), and extraction solvent and preparation ^{5,6,7Reference 5Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neuronsView study →Reference 6Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →}. A UPLC-MS/MS survey of 28 commercial kava products found large variation in both total and relative kavalactone abundance, and label kavalactone claims that could differ from measured content by up to ~90% ^{7Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →} — so any single percentage figure for DMY is preparation-dependent rather than a fixed property of the plant.

Discovery & Synthesis

Desmethoxyyangonin was characterised as one of the classic six kavalactones during the twentieth-century phytochemical work that resolved kava root’s active styryl-pyrones; it takes its name from being the des-methoxy analogue of yangonin (yangonin minus one aromatic methoxy group). Modern production of the isolate is not from plant extraction at scale but from biosynthesis and synthesis: the kava styrylpyrone pathway has been reconstituted de novo in Saccharomyces cerevisiae, yielding desmethoxyyangonin (titre ~1.28 µM in the first-generation strain) among diverse plant styrylpyrones — a route aimed at sustainable, standardised supply of individual kavalactones for research ^{13Reference 13Wu Y et al. · 2022De novo biosynthesis of diverse plant-derived styrylpyrones in Saccharomyces cerevisiaeView study →}.

Patents: not yet researched.

Toxicity & Safety

Desmethoxyyangonin carries a moderate flag. The reason is not direct organ toxicity of the molecule — it is DMY’s pharmacology: as the most potent kavalactone MAO-B inhibitor ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →} with a dopaminergic action ^{2Reference 2Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}, and as a member of the CYP-inhibiting, centrally sedative kavalactone class ^{7,9Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →Reference 9Bian T et al. · 2020Kava as a clinical nutrient: promises and challengesView study →}, it sits at the centre of kava’s interaction profile even though it is not kava’s hepatotoxic culprit.

Kava Root Kavalactones vs. Aerial-Part Hepatotoxins

The single most important safety point for reading a kavalactone page: the rare hepatotoxicity historically associated with some kava products does not track the root kavalactones such as DMY. In HepG2 hepatocytes the aerial-part alkaloid pipermethystine — concentrated in leaves and stem peelings, not the traditional root beverage — was markedly more cytotoxic than the kavalactones ^{10Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}. Reviews of kava liver injury point instead to the chalcone flavokavains (notably flavokavain B), pipermethystine, and mould/processing contaminants as the leading candidate culprits ^{11Reference 11Teschke R et al. · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}, and in mice it was flavokavains A and B — not the kavalactone dihydromethysticin — that potentiated acetaminophen-induced liver injury ^{12Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}. The practical corollary is the traditional one: peeled-root, noble-cultivar, aqueous kava minimises the aerial-part and chalcone load, and the well-tolerated GAD trial of aqueous whole-root kava saw no liver-function signal over its course ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}. DMY is a root kavalactone, on the safer side of that divide.

Safety at a Glance

⚠️ Moderate toxicityDrug interactions

• DMY is a root kavalactone, not kava’s hepatotoxin. The liver signal tracks aerial-part pipermethystine and the chalcone flavokavains, not the root styryl-pyrones ^{10,11,12Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →Reference 11Teschke R et al. · 2011Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}.
• It is an MAO-B inhibitor. As the most potent kavalactone inhibitor of MAO-B ^{1Reference 1Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →}, concentrated kava could in principle interact with monoaminergic drugs and MAO-sensitive substrates; the effect is reversible, but the caution is real.
• Additive CNS sedation. Kavalactones are centrally active; combining kava with alcohol, benzodiazepines or other CNS depressants can compound sedation ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}.
• CYP450 herb–drug interactions. Kavalactones inhibit several cytochrome-P450 enzymes, kava’s documented interaction mechanism — relevant with CYP-metabolised medications ^{7,9Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →Reference 9Bian T et al. · 2020Kava as a clinical nutrient: promises and challengesView study →}.
• Preparation and cultivar matter. Content varies widely and labels can misstate it; noble-cultivar peeled-root aqueous preparations are the traditionally safer exposure ^{7,10Reference 7Mamallapalli J et al. · 2022Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MSView study →Reference 10Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}.

Reproductive and developmental safety of isolated desmethoxyyangonin is not characterised, and pregnancy/lactation decisions belong to the kava herb page where intake is decided, not to this molecule page.

Dosage

There is no established dose for isolated desmethoxyyangonin — it is consumed only as a minor fraction of whole kava. The meaningful human figure is kava’s total kavalactone dose: traditional aqueous root beverages, and standardised extracts dosed by kavalactone content, with anxiety trials using roughly 120–240 mg of kavalactones per day ^{8Reference 8Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →}.

The isolate values are in-vitro and animal research figures for the molecule, and the kavalactone dose is the whole-plant research range — neither is a personal recommendation.

References

1. Uebelhack R, Franke L, Schewe HJ (1998). Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry. https://pubmed.ncbi.nlm.nih.gov/9832350/
2. Baum SS, Hill R, Rommelspacher H (1998). Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry. https://pubmed.ncbi.nlm.nih.gov/9829291/
3. Chua HC, Christensen ET, Hoestgaard-Jensen K, et al. (2016). Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanism. PLoS One. https://pubmed.ncbi.nlm.nih.gov/27332705/
4. Gleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na⁺-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/
5. Magura EI, Kopanitsa MV, Gleitz J, et al. (1997). Kava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neurons. Neuroscience. https://pubmed.ncbi.nlm.nih.gov/9300426/
6. Wang J, Qu W, Bittenbender HC, et al. (2015). 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. https://pubmed.ncbi.nlm.nih.gov/25694734/
7. Mamallapalli J, Kanumuri SRR, Corral P, et al. (2022). Characterization of different forms of kava (Piper methysticum) products by UPLC-MS/MS. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/34839465/
8. Sarris J, Stough C, Bousman CA, et al. (2013). Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. Journal of Clinical Psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/23635869/
9. Bian T, Corral P, Wang Y, et al. (2020). Kava as a clinical nutrient: promises and challenges. Nutrients. https://pubmed.ncbi.nlm.nih.gov/33027883/
10. Nerurkar PV, Dragull K, Tang CS (2004). In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones. Toxicological Sciences. https://pubmed.ncbi.nlm.nih.gov/14737001/
11. Teschke R, Qiu SX, Lebot V (2011). Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Digestive and Liver Disease. https://pubmed.ncbi.nlm.nih.gov/21377431/
12. Narayanapillai SC, Leitzman P, O’Sullivan MG, et al. (2014). Flavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice. Chemical Research in Toxicology. https://pubmed.ncbi.nlm.nih.gov/25185080/
13. Wu Y, Chen MN, Li S (2022). De novo biosynthesis of diverse plant-derived styrylpyrones in Saccharomyces cerevisiae. Metabolic Engineering Communications. https://pubmed.ncbi.nlm.nih.gov/35287355/

View all 13 references▾