6-Hydroxy-7-methoxycoumarin

6-Hydroxy-7-methoxycoumarin at a Glance

6-Hydroxy-7-methoxycoumarin, almost always called isoscopoletin, is a simple plant hydroxycoumarin. It carries a hydroxyl at position 6 and a methoxy at position 7 of the coumarin ring — the exact mirror of scopoletin (7-hydroxy-6-methoxycoumarin), with which it is easily and often confused. It occurs as a minor constituent of Chinese mugwort (Artemisia argyi), Mexican tarragon (Tagetes lucida), Chinese ash bark (Fraxinus chinensis) and various buttercups (Ranunculus spp.), and it can form in the body as a demethylation product of the dimethoxycoumarin scoparone ^{1,2Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →Reference 2Ruan C et al. · 2024Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteinsView study →}.

Its pharmacology is entirely preclinical — there are no human trials of the isolated molecule. The best-defined signals are a genuinely potent, low-micromolar antiproliferative effect on leukaemia and liver-cancer cell lines in vitro ^{1,2Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →Reference 2Ruan C et al. · 2024Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteinsView study →}, and an anti-inflammatory action in cultured skin and immune cells ^{3,4Reference 3Seo DY et al. · 2024Effect of isoscopoletin on cytokine expression in HaCaT keratinocytes and RBL-2H3 basophils: preliminary studyView study →Reference 4Chang HC et al. · 2020Secoiridoid glucosides and anti-inflammatory constituents from the stem bark of Fraxinus chinensisView study →}. Weaker antiviral (hepatitis B) and antimicrobial signals round out a thin but real evidence base ^{5,6Reference 5Li H et al. · 2005Evaluation of antiviral activity of compounds isolated from Ranunculus sieboldii and Ranunculus sceleratusView study →Reference 6Céspedes CL et al. · 2006Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida)View study →}.

Unlike the furanocoumarins it shares a chemical family with (psoralen, bergapten, imperatorin), isoscopoletin has no furan ring and is not phototoxic.

Isoscopoletin vs. Scopoletin — The Isomer Distinction

This is the single most important point about the molecule. Isoscopoletin and scopoletin are positional isomers: both are 6,7-disubstituted coumarins carrying one hydroxyl and one methoxy group, but the two substituents are swapped.

• Scopoletin = 7-hydroxy-6-methoxycoumarin (hydroxyl at 7, methoxy at 6).
• Isoscopoletin = 6-hydroxy-7-methoxycoumarin (hydroxyl at 6, methoxy at 7).

They are frequently isolated from the same plants — both appear together in Artemisia argyi and in Mexican tarragon ^{1,6Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →Reference 6Céspedes CL et al. · 2006Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida)View study →} — and both derive from the same parent diol, esculetin (6,7-dihydroxycoumarin), by methylation of one hydroxyl or the other. Scopoletin is by far the more studied of the pair (its own page covers a large preclinical literature on xanthine-oxidase/urate lowering and NF-κB/Nrf2 signalling), so it is tempting to read scopoletin’s data onto isoscopoletin. Do not. The activities described below are attributed to isoscopoletin only where the source tested and named this isomer — most usefully in the one head-to-head study, where the two isomers were isolated side by side and assayed separately ^{1Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →}.

What It's Used For

All of the evidence is in vitro, on the isolated molecule, and none of it has reached animals-in-disease models or people. The strongest thread is anticancer cell-proliferation data; the anti-inflammatory work is next; antiviral and antimicrobial signals are single-study or screen-level.

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 application here is in-vitro isolate data, so scores stay low by design.

01Antiproliferative / AnticancerShaky38%Two in-vitro studies: low-µM IC50 in leukaemia (incl. MDR line) + glycolysis mechanism in liver cancer ^{1,2Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →Reference 2Ruan C et al. · 2024Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteinsView study →}

02Anti-InflammatoryShaky32%Two in-vitro studies: cytokine/chemokine suppression in keratinocytes; neutrophil & LPS-NO inhibition ^{3,4Reference 3Seo DY et al. · 2024Effect of isoscopoletin on cytokine expression in HaCaT keratinocytes and RBL-2H3 basophils: preliminary studyView study →Reference 4Chang HC et al. · 2020Secoiridoid glucosides and anti-inflammatory constituents from the stem bark of Fraxinus chinensisView study →}

03Antiviral (Hepatitis B)Shaky22%Single in-vitro screen — HBV replication inhibition among Ranunculus compounds ^{5Reference 5Li H et al. · 2005Evaluation of antiviral activity of compounds isolated from Ranunculus sieboldii and Ranunculus sceleratusView study →}

04AntimicrobialShaky16%Isolated and assayed within a coumarin antibacterial/antifungal screen of Mexican tarragon ^{6Reference 6Céspedes CL et al. · 2006Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida)View study →}

Mechanisms

Everything in this table is in-vitro. The load-bearing distinction is that these are isoscopoletin’s own measured effects — they are not borrowed from its isomer scopoletin, whose signature xanthine-oxidase/urate-lowering activity is not among them.

Pharmacokinetics

There is essentially no dedicated pharmacokinetic dataset for isoscopoletin. As a small, lipophilic 6,7-disubstituted coumarin it would be expected to absorb reasonably and undergo hepatic phase-I/II metabolism (glucuronidation/sulfation of the free 6-hydroxyl), but oral bioavailability, plasma levels and half-life have not been characterised for the isolate. What is documented is the reverse relationship: isoscopoletin arises as one of the primary O-demethylation metabolites of scoparone (6,7-dimethoxycoumarin), so some systemic exposure to isoscopoletin can occur after intake of scoparone-rich material ^{2,7Reference 2Ruan C et al. · 2024Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteinsView study →Reference 7Hui Y et al. · 2020Scoparone as a therapeutic drug in liver diseases: pharmacology, pharmacokinetics and molecular mechanisms of actionView study →}. The absence of PK data is itself the caveat: the striking low-micromolar in-vitro IC50s cannot be assumed to translate to achievable tissue concentrations in vivo.

Clinical Trials

There are no clinical trials of isoscopoletin — completed, ongoing or terminated. The entire evidence base is preclinical cell-culture work.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for a trace phytochemical, isoscopoletin’s evidence is almost entirely on the purified isolate, not on whole extracts — the leukaemia and liver-cancer work used the isolated compound with defined IC50s ^{1,2Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →Reference 2Ruan C et al. · 2024Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteinsView study →}, as did the keratinocyte study ^{3Reference 3Seo DY et al. · 2024Effect of isoscopoletin on cytokine expression in HaCaT keratinocytes and RBL-2H3 basophils: preliminary studyView study →}. That is a methodological strength (the activity is attributable to the molecule, not an extract matrix). The limitation is the opposite of the usual one: because there is no whole-plant or animal-model bridge and no human intake data, it is unknown whether meaningful amounts of isoscopoletin are ever delivered to relevant tissues from any of its (minor) botanical sources. The one whole-plant screen — Mexican tarragon — tested it as an isolated compound within a panel rather than as a plant preparation ^{6Reference 6Céspedes CL et al. · 2006Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida)View study →}.

Prevalence in Nature

Isoscopoletin is a minor, scattered coumarin rather than a bulk plant metabolite. It has been isolated from the leaves of Chinese mugwort (Artemisia argyi), where it co-occurs with scopoletin ^{1Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →}; from the aerial parts of Mexican tarragon (Tagetes lucida) alongside six other coumarins (esculetin, umbelliferone, scoparone, herniarin, scopoletin and 7,8-dihydroxycoumarin) ^{6Reference 6Céspedes CL et al. · 2006Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida)View study →}; from the stem bark of Chinese ash (Fraxinus chinensis) ^{4Reference 4Chang HC et al. · 2020Secoiridoid glucosides and anti-inflammatory constituents from the stem bark of Fraxinus chinensisView study →}; and from buttercups (Ranunculus sieboldii, R. sceleratus) ^{5Reference 5Li H et al. · 2005Evaluation of antiviral activity of compounds isolated from Ranunculus sieboldii and Ranunculus sceleratusView study →}. It is also reported from Viola species and citrus. Across these sources it is present at trace levels; no clean quantitative abundance (% dry weight) figure is well established for the isolate, so its natural concentrations remain poorly quantified.

Discovery & Synthesis

Isoscopoletin (CAS 776-86-3) is a long-known natural coumarin — the 6-hydroxy-7-methoxy positional isomer of scopoletin and the 7-O-methyl ether of esculetin (hence the synonym 7-methoxyesculetin). Its precise first isolation is not well documented in the accessible literature, reflecting its status as a minor constituent repeatedly re-encountered in coumarin surveys rather than a molecule with a landmark discovery. Synthetically it is straightforward to reach by selective mono-O-methylation of esculetin at the 7-position (the complementary methylation gives scopoletin), and it also arises biologically as an O-demethylation product of scoparone ^{2,7Reference 2Ruan C et al. · 2024Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteinsView study →Reference 7Hui Y et al. · 2020Scoparone as a therapeutic drug in liver diseases: pharmacology, pharmacokinetics and molecular mechanisms of actionView study →}. It is available commercially as a purified reference standard for research use; manufacture is by extraction or partial synthesis rather than any large-scale industrial route.

Patents: not yet researched.

Toxicity & Safety

Isoscopoletin carries a low flag. It is a simple hydroxycoumarin occurring at trace levels in edible and medicinal plants (mugwort, Mexican tarragon, citrus), it lacks the furan ring responsible for furanocoumarin phototoxicity, and no specific toxicity alerts have been reported for it. That said, the low rating reflects an absence of adverse findings plus a benign structure, not a completed safety dossier — there is no dedicated repeat-dose, genotoxicity or reproductive-toxicology package for the isolated molecule.

Safety at a Glance

✅ Low / no toxicity

• Not phototoxic. Unlike the furanocoumarins in its chemical family (psoralen, bergapten, imperatorin), isoscopoletin has no furan ring and does not photosensitise skin.
• Trace occurrence in edible/medicinal plants. Dietary and herbal exposure is at low background levels, with no reported toxicity signal.
• No dedicated toxicology or human data. Genotoxicity, repeat-dose and reproductive endpoints have not been characterised for the isolate; the low rating is provisional.
• Do not infer safety — or activity — from scopoletin. It is a different molecule; interactions and effects have not been studied for isoscopoletin specifically.

No reproductive- or developmental-toxicity dataset exists for isolated isoscopoletin, and drug-interaction potential (CYP/UGT/transporter effects) has not been assessed. Pregnancy and lactation decisions belong to the herb or product where intake is actually decided, not to this molecule page.

Dosage

There is no established human dose and no clinical use. Every figure in the literature is an in-vitro concentration: the antiproliferative IC50s sit at 1.6–4.0 µM (leukaemia/MDR cells) ^{1Reference 1Adams M et al. · 2006Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyiView study →}, the anti-inflammatory work used ≤40 µM in cultured cells ^{3Reference 3Seo DY et al. · 2024Effect of isoscopoletin on cytokine expression in HaCaT keratinocytes and RBL-2H3 basophils: preliminary studyView study →}, and the Fraxinus neutrophil assays reported IC50s in the low µg/mL range ^{4Reference 4Chang HC et al. · 2020Secoiridoid glucosides and anti-inflammatory constituents from the stem bark of Fraxinus chinensisView study →}. These are laboratory concentrations used to characterise the molecule, not doses studied in — or recommended for — people.

References

1. Adams M, Efferth T, Bauer R (2006). Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyi. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/16881019/
2. Ruan C, Wang C, Gu J, Zhu Z (2024). Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteins. PLoS One. https://pubmed.ncbi.nlm.nih.gov/39509399/
3. Seo DY, Park JW, Kim SH, Oh SR, Han SB, Kwon OK, Ahn KS (2024). Effect of isoscopoletin on cytokine expression in HaCaT keratinocytes and RBL-2H3 basophils: preliminary study. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/39000019/
4. Chang HC, Wang SW, Chen CY, Hwang TL, Cheng MJ, Sung PJ, Liao KW, Chen JJ (2020). Secoiridoid glucosides and anti-inflammatory constituents from the stem bark of Fraxinus chinensis. Molecules. https://pubmed.ncbi.nlm.nih.gov/33327368/
5. Li H, Zhou C, Pan Y, et al. (2005). Evaluation of antiviral activity of compounds isolated from Ranunculus sieboldii and Ranunculus sceleratus. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/16395649/
6. Céspedes CL, Avila JG, Martínez A, Serrato B, Calderón-Mugica JC, Salgado-Garciglia R (2006). Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida). Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/19127719/
7. Hui Y, Wang X, Yu Z, et al. (2020). Scoparone as a therapeutic drug in liver diseases: pharmacology, pharmacokinetics and molecular mechanisms of action. Pharmacological Research. https://pubmed.ncbi.nlm.nih.gov/32877694/

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