6,7,8-Trimethoxycoumarin

6,7,8-Trimethoxycoumarin at a Glance

6,7,8-Trimethoxycoumarin is a simple trimethoxy coumarin — a benzopyranone with three methoxy groups — most consistently reported from the aerial parts of Mexican tarragon (Tagetes lucida), the aromatic Mexican herb also called yauhtli or pericón ^{1,2Reference 1Santibáñez A et al. · 2023Dose-effect determination of a neuroprotector fraction standardized in coumarins of Tagetes lucida and bioavailabilityView study →Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →}. Structurally it is the dimethyl ether of fraxetin, which is why the pharmacology literature usually calls it dimethylfraxetin (see below) ^{1Reference 1Santibáñez A et al. · 2023Dose-effect determination of a neuroprotector fraction standardized in coumarins of Tagetes lucida and bioavailabilityView study →}.

Importantly, it is an ordinary coumarin, not a furanocoumarin: it has no furan ring fused to the benzopyranone, so it does not carry the photosensitising / phototoxic liability of psoralen-type furanocoumarins.

The evidence base is entirely preclinical. Across a handful of studies from a single Mexican research programme, the isolated molecule shows vasorelaxant/antihypertensive, neuroprotective, and antipsychotic-like activity in animal models, and a semi-synthetic screen ranks it among the gastroprotective coumarins with low toxicity ^{2,3,4,5Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →Reference 3Castro-Martínez G et al. · 2023Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizoneView study →Reference 4Porras-Dávila SL et al. · 2022Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidolView study →Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}. There are no human data for any use.

Dimethylfraxetin: The Same Molecule

The most important thing to know about this compound is a naming collision: “dimethylfraxetin” and “6,7,8-trimethoxycoumarin” are the same molecule.

Fraxetin is 7,8-dihydroxy-6-methoxycoumarin. Methylating both of its free hydroxyls (at C-7 and C-8) converts them to methoxy groups, giving 6,7,8-trimethoxycoumarin (fraxetin dimethyl ether). PubChem resolves both names to the identical structure — 6,7,8-trimethoxychromen-2-one, C₁₂H₁₂O₅, CAS 6035-49-0.

This matters because the Tagetes lucida pharmacology papers split the work across both names: the vasorelaxant study calls it 6,7,8-trimethoxycoumarin ^{2Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →}, while the neuroprotective and antipsychotic-like studies call it dimethylfraxetin (abbreviated “DF”) ^{3,4Reference 3Castro-Martínez G et al. · 2023Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizoneView study →Reference 4Porras-Dávila SL et al. · 2022Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidolView study →}. Read as one molecule, the evidence is broader than either name suggests on its own. It also means any separate “dimethylfraxetin” entry describes the same compound and must not be duplicated.

What It's Used For

All of the evidence below is preclinical — isolated tissue, or oral/behavioural experiments in mice and rats. Much of it comes from Tagetes lucida research, where 6,7,8-trimethoxycoumarin is studied both as an isolate and as a component of a standardised coumarin fraction, alongside its sibling coumarins scoparone (6,7-dimethoxycoumarin) and herniarin (7-methoxycoumarin).

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. Every row here is preclinical only; no human outcome exists for any application, so scores stay low.

01Vasorelaxant / antihypertensiveShaky34%Isolated aorta + hypertensive-rat model; named main active metabolite ^{2Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →}

02Neuroprotective / anti-neuroinflammatoryShaky30%Cuprizone demyelination model, one study (as dimethylfraxetin) ^{3Reference 3Castro-Martínez G et al. · 2023Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizoneView study →}

03Antipsychotic-likeShaky26%Ketamine-psychosis behavioural model, one study ^{4Reference 4Porras-Dávila SL et al. · 2022Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidolView study →}

04GastroprotectiveShaky24%Rodent gastric-lesion screen of scoparone derivatives ^{5Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}

Mechanisms

The vascular mechanism (NO/cGMP + Ca²⁺ block) is the load-bearing pharmacology; the carbonic-anhydrase result is a class-level in-vitro observation for natural coumarins, not a validated therapeutic mechanism for this molecule.

Pharmacokinetics

No dedicated pharmacokinetic profile (oral bioavailability, plasma half-life, metabolism, active metabolites) has been characterised for isolated 6,7,8-trimethoxycoumarin in the sources reviewed. The most relevant data are indirect: a standardised T. lucida coumarin fraction — of which this molecule is one component — has been the subject of pharmacokinetic study ^{1Reference 1Santibáñez A et al. · 2023Dose-effect determination of a neuroprotector fraction standardized in coumarins of Tagetes lucida and bioavailabilityView study →}, and an in-vitro assay found the isolate causes only minimal CYP3A4/CYP2C9 inhibition, suggesting a low drug-interaction footprint ^{5Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}. As a fully methylated coumarin it lacks free hydroxyls for direct glucuronidation/sulfation, so O-demethylation would be expected to dominate its metabolism — but this is inference, not measured data. This is the page’s clearest data hole.

Clinical Trials

There are no registered or published human clinical trials of 6,7,8-trimethoxycoumarin / dimethylfraxetin as an isolated compound. All evidence is preclinical.

Last checked: July 2026.

Isolate vs. Plant Studies

The evidence sits between isolate and plant, and the distinction is honest to draw. The gastroprotective and carbonic-anhydrase findings use the pure compound (semi-synthetic derivative screen and a natural-product library, respectively) ^{5,6Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →Reference 6Davis RA et al. · 2013Natural product coumarins that inhibit human carbonic anhydrasesView study →}. The vasorelaxant, neuroprotective and antipsychotic-like findings come from Tagetes lucida research where the molecule is named as an active constituent but is frequently tested alongside a whole extract or standardised coumarin fraction, and alongside its siblings scoparone and herniarin ^{2,3,4Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →Reference 3Castro-Martínez G et al. · 2023Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizoneView study →Reference 4Porras-Dávila SL et al. · 2022Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidolView study →}. So while 6,7,8-trimethoxycoumarin is repeatedly implicated as an active molecule, much of the in-vivo signal cannot be cleanly separated from the plant matrix — a caveat that applies to almost all of the Tagetes coumarin literature.

Prevalence in Nature

6,7,8-Trimethoxycoumarin is a minor coumarin with a scattered natural distribution. Its best-documented source is the aerial parts of Mexican tarragon (Tagetes lucida), where it is one of several coumarins — with scoparone, herniarin, scopoletin and esculetin — that make the plant’s coumarin fraction pharmacologically interesting ^{1,2,3Reference 1Santibáñez A et al. · 2023Dose-effect determination of a neuroprotector fraction standardized in coumarins of Tagetes lucida and bioavailabilityView study →Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →Reference 3Castro-Martínez G et al. · 2023Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizoneView study →}. It has also been reported from Viola (V. yedoensis) and Euphorbia (E. quinquecostata) species, generally as a minor constituent.

No quantified concentration (% dry weight or mg/g) is reported for this compound in the sources reviewed; where it is measured it appears within a coumarin fraction rather than as an individually quantified peak. Reported citrus-peel / Artemisia occurrence was not verifiable in the sources checked and is not claimed here. Filling in a real concentration figure — and confirming genera beyond Tagetes — is a gap for a later pass.

Discovery & Synthesis

6,7,8-Trimethoxycoumarin has been known for decades as fraxetin dimethyl ether — the fully methylated relative of the plant coumarins fraxetin and scoparone — but a discrete first-isolation date and discoverer are not well documented in the accessible literature. It carries CAS 6035-49-0.

Because it is simply the trimethyl-oxygenated coumarin, it is readily obtained by exhaustive O-methylation of a hydroxy/methoxy coumarin precursor (e.g. methylating fraxetin’s free hydroxyls, or building it from a trihydroxy/trimethoxy benzaldehyde via a Pechmann/Knoevenagel coumarin condensation). In practice the compound is sold as a reference standard isolated from plant material or prepared semi-synthetically; there is no large-scale natural-extraction industry around it, and the pharmacology studies use plant-isolated or synthesised material ^{2,5Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}.

Patents: not yet researched.

Toxicity & Safety

6,7,8-Trimethoxycoumarin carries a low flag. The direct evidence is limited but reassuring as far as it goes: a rodent screen reported low acute oral toxicity and only minimal effects on the major drug-metabolising enzymes CYP3A4/CYP2C9, implying a low drug-interaction risk ^{5Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}. Critically, as a simple coumarin (not a furanocoumarin) it lacks the fused furan ring that makes psoralen-type molecules photo-toxic, so it is not expected to cause phototoxicity or photosensitisation.

The important caveat is the absence of data, not the presence of harm: there is no human safety experience, no repeat-dose or reproductive-toxicity dataset, and no genotoxicity package for the isolated compound. Coumarins as a class can raise hepatotoxicity questions (driven largely by the parent coumarin’s metabolism), but no specific hepatotoxic signal has been characterised for this trimethoxy derivative.

Safety at a Glance

✅ Low / no toxicity

• Not a furanocoumarin. No fused furan ring, so no expected phototoxicity/photosensitisation — unlike psoralen, bergapten or xanthotoxin.
• Low measured toxicity signal. Low acute oral toxicity in mice and minimal CYP3A4/CYP2C9 inhibition in the one screen that assessed it ^{5Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}.
• Animal data only. No human safety experience; all findings are preclinical and largely from a single research group.
• No repeat-dose, reproductive or genotoxicity data for the isolate; pregnancy/lactation and long-term safety are simply uncharacterised.

Dosage

There is no established human dose. Every figure in the literature is from animal research — oral milligram-per-kilogram dosing in mouse and rat models of hypertension, demyelination, ketamine psychosis and gastric injury — where the compound was usually given as an isolate or as part of a standardised Tagetes lucida coumarin preparation ^{2,3,4,5Reference 2Estrada-Soto S et al. · 2021Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolitesView study →Reference 3Castro-Martínez G et al. · 2023Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizoneView study →Reference 4Porras-Dávila SL et al. · 2022Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidolView study →Reference 5Son DJ et al. · 2015AnimalGastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodentsView study →}. These are experimental doses used to probe mechanism, not human dosing guidance, and they do not translate directly to people. This is not a personal recommendation.

References

1. Santibáñez A, et al. (2023). Dose-effect determination of a neuroprotector fraction standardized in coumarins of Tagetes lucida and bioavailability. Pharmaceutics. https://pubmed.ncbi.nlm.nih.gov/36986828/
2. Estrada-Soto S, et al. (2021). Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolites. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/32961278/
3. Castro-Martínez G, et al. (2023). Effects of five coumarins and standardized extracts from Tagetes lucida Cav. on motor impairment and neuroinflammation induced with cuprizone. Pharmaceuticals (Basel). https://pubmed.ncbi.nlm.nih.gov/37895861/
4. Porras-Dávila SL, et al. (2022). Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidol. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/36297813/
5. Son DJ, et al. (2015). Gastroprotective efficacy and safety evaluation of scoparone derivatives on experimentally induced gastric lesions in rodents. Nutrients. https://pubmed.ncbi.nlm.nih.gov/25781220/
6. Davis RA, et al. (2013). Natural product coumarins that inhibit human carbonic anhydrases. Bioorganic & Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/22892213/

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