7,8-Dihydroxycoumarin

7,8-Dihydroxycoumarin at a Glance

7,8-Dihydroxycoumarin, almost always called daphnetin, is a simple catechol-type coumarin — two adjacent hydroxyl groups on the coumarin ring — first drawn from the bark of Daphne species, the genus that gives it its name ^{2Reference 2Zhang L et al. · 2025ReviewInvestigating the Therapeutic Potential and Molecular Mechanisms of Daphnetin: A Comprehensive ReviewView study →}. It also occurs in Stellera chamaejasme, Mexican tarragon (Tagetes lucida) and a scattering of other plants ^{3,14Reference 3Hang S et al. · 2022Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic PotentialView study →Reference 14Han S et al. · 2020Daphne giraldii Nitsche (Thymelaeaceae): Phytochemistry, pharmacology and medicinal usesView study →}.

For a minor coumarin it carries an unusually broad and genuinely repeated preclinical record: immunomodulation in rheumatoid-arthritis models, a decades-old Chinese antimalarial research line, neuroprotection, and a recognised role as a protein-kinase-inhibitor scaffold in medicinal chemistry ^{1,7,9Reference 1Javed M et al. · 2022Daphnetin: A bioactive natural coumarin with diverse therapeutic potentialsView study →Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →Reference 9Yang EB et al. · 1999Daphnetin, one of coumarin derivatives, is a protein kinase inhibitorView study →}. That breadth is real, but it comes with a hard limit — every study is a cell line, an isolated enzyme, or a rodent. There are no human trials of the isolate, and the reviews that call its safety profile “promising” are speaking from animal data, not clinical exposure ^{1Reference 1Javed M et al. · 2022Daphnetin: A bioactive natural coumarin with diverse therapeutic potentialsView study →}.

Two disciplines apply, as for its sibling coumarins: daphnetin is not a 4-hydroxycoumarin/warfarin-type anticoagulant, and it is not the hepatotoxic fragrance “coumarin.” It is also a plain dihydroxycoumarin, not a furanocoumarin, so it does not carry the phototoxic/photosensitising liability of psoralen-type molecules.

Daphnetin vs. Esculetin — The Two Catechol Coumarins

Daphnetin is best understood next to its close isomer esculetin (6,7-dihydroxycoumarin). Both are catechol coumarins — a pair of adjacent (“ortho”) hydroxyls that makes each a strong direct radical scavenger and a metal chelator, chemistry that mono-hydroxy coumarins like umbelliferone and scopoletin lack.

The difference is where the two hydroxyls sit:

• Esculetin = 6,7-dihydroxycoumarin — the aglycone of esculin, with its signature target being 5-lipoxygenase.
• Daphnetin = 7,8-dihydroxycoumarin — the 8-hydroxyl is the distinctive feature: structure–activity work found that the C8 hydroxyl is required for daphnetin’s protein-kinase-inhibitory activity, which esculetin does not share to the same degree ^{9Reference 9Yang EB et al. · 1999Daphnetin, one of coumarin derivatives, is a protein kinase inhibitorView study →}.

So while the two isomers overlap on class-shared antioxidant chemistry, daphnetin’s more distinctive pharmacology — kinase inhibition and the antimalarial line — tracks that 7,8- (rather than 6,7-) substitution pattern. The catechol also matters mechanistically to the antimalarial story: daphnetin’s antiplasmodial activity is blocked by iron, consistent with an iron-chelation mechanism ^{7Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →}.

What It's Used For

The evidence machinery below is entirely preclinical. Daphnetin’s strength is breadth with repetition — several independent groups return to arthritis and malaria — but its ceiling is the total absence of human isolate data.

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. There is no human isolate data, so every score is capped low by design; the ranking reflects how repeated and mechanistically defined the preclinical signal is.

01Anti-Inflammatory / Anti-ArthriticShaky44%Repeated collagen-induced arthritis rat studies; Treg/Th17 + demethylation mechanisms ^{4,5,6Reference 4Yao R et al. · 2011Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritisView study →Reference 5Tu L et al. · 2012The therapeutic effects of daphnetin in collagen-induced arthritis involve its regulation of Th17 cellsView study →Reference 6Shu K et al. · 2014Therapeutic effect of daphnetin on the autoimmune arthritis through demethylation of proapoptotic genes in synovial cellsView study →}

02Antimalarial (Schizontocidal)Shaky38%Decades of in-vitro + mouse Plasmodium work; iron-chelation mechanism ^{7,8Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →Reference 8Wang QM et al. · 2004Comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasitesView study →}

03NeuroprotectiveShaky32%NMDA-excitotoxicity + cerebral-ischaemia models; microglial suppression ^{10,11Reference 10Yang J et al. · 2014Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicityView study →Reference 11Yu W et al. · 2014Daphnetin attenuates microglial activation and proinflammatory factor production via multiple signaling pathwaysView study →}

04Kinase Inhibition / AnticancerShaky30%EGFR/PKA/PKC inhibition in vitro; renal-carcinoma differentiation ^{9,15Reference 9Yang EB et al. · 1999Daphnetin, one of coumarin derivatives, is a protein kinase inhibitorView study →Reference 15Finn GJ et al. · 2004Daphnetin induced differentiation of human renal carcinoma cells and its mediation by p38 mitogen-activated protein kinaseView study →}

05Antioxidant (Catechol)Shaky26%Class-shared catechol scavenging + Nrf2/HO-1 induction ^{12Reference 12Singh L et al. · 2021Mechanistic interplay of various mediators involved in mediating the neuroprotective effect of daphnetinView study →}

Mechanisms

The load-bearing points are the iron-chelation antimalarial mechanism and the C8-hydroxyl-dependent kinase inhibition — both trace to daphnetin’s specific 7,8-dihydroxy (catechol) substitution, which distinguishes it from 6,7-esculetin.

Pharmacokinetics

Daphnetin’s human pharmacokinetics are poorly characterised — a real limit on interpreting the in-vitro potencies above. What exists is rodent: after oral dosing it is absorbed but subject to rapid phase-II conjugation (as expected for a catechol/phenolic), and a rat study found that co-administration of Glycyrrhiza (licorice) constituents such as liquiritin raised daphnetin’s AUC and Cmax roughly 1.5-fold, implying otherwise limited/variable oral exposure that herb combinations can modulate ^{13Reference 13Zhang Y et al. · 2014AnimalThe effects of Glycyrrhizae uralensis and its major bioactive components on pharmacokinetics of daphnetin in Cortex daphnes in ratsView study →}. No validated human oral bioavailability, half-life or active-metabolite data are published for the isolate.

Clinical Trials

There are no clinical trials of isolated 7,8-dihydroxycoumarin (daphnetin). The entire evidence base is preclinical; the closest to “applied” work is the historical Chinese antimalarial development program, which did not mature into a registered drug ^{7,8Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →Reference 8Wang QM et al. · 2004Comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasitesView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for a minor coumarin, most daphnetin research is on the isolate, not the whole plant — the CIA-arthritis studies, the antimalarial screens and the kinase-inhibition work all use purified/recrystallised daphnetin ^{6,7,9Reference 6Shu K et al. · 2014Therapeutic effect of daphnetin on the autoimmune arthritis through demethylation of proapoptotic genes in synovial cellsView study →Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →Reference 9Yang EB et al. · 1999Daphnetin, one of coumarin derivatives, is a protein kinase inhibitorView study →}. That is a methodological strength (the effects are attributable to the molecule) but not a clinical one: none of it is in humans. Where the plant matters is provenance — daphnetin is a marker/active of Daphne bark preparations (Cortex Daphnes) and Stellera chamaejasme in traditional Chinese use, and of Mexican tarragon’s coumarin fraction ^{3,14Reference 3Hang S et al. · 2022Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic PotentialView study →Reference 14Han S et al. · 2020Daphne giraldii Nitsche (Thymelaeaceae): Phytochemistry, pharmacology and medicinal usesView study →} — but the pharmacology record is the isolated compound’s, in models.

Prevalence in Nature

Daphnetin is a Thymelaeaceae-family coumarin, most associated with the bark of Daphne species — D. odora, D. giraldii and D. genkwa — where it is a characteristic constituent of the crude drug Cortex Daphnes (zushima) ^{4,14Reference 4Yao R et al. · 2011Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritisView study →Reference 14Han S et al. · 2020Daphne giraldii Nitsche (Thymelaeaceae): Phytochemistry, pharmacology and medicinal usesView study →}. It is also a notable component of Stellera chamaejasme (langdu), reviewed specifically as a daphnetin source ^{3Reference 3Hang S et al. · 2022Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic PotentialView study →}. Beyond the Thymelaeaceae it is reported among the coumarins of Mexican tarragon (Tagetes lucida) aerial parts and in Eucommia ulmoides, and has been picked up as a minor anti-inflammatory constituent in dietary plants such as tomato ^{1Reference 1Javed M et al. · 2022Daphnetin: A bioactive natural coumarin with diverse therapeutic potentialsView study →}. Quantitative concentration figures for daphnetin as a percent of dry weight are sparse — the occurrence is well attested, the numbers are not well tabulated (a gap).

Discovery & Synthesis

Daphnetin takes its name directly from Daphne, the shrub genus (and, ultimately, the Greek nymph turned laurel) from whose bark the coumarin was first obtained; a precise first-isolation date is not well documented in the accessible literature. Its modern research profile began in China, where daphnetin was investigated as an antimalarial “schizontocide” through the 1980s–2000s and, in parallel, entered arthritis and immunology research ^{1,7Reference 1Javed M et al. · 2022Daphnetin: A bioactive natural coumarin with diverse therapeutic potentialsView study →Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →}. Total synthesis of daphnetin is not prominently documented as a landmark route, but as a small dihydroxycoumarin it is synthetically accessible (e.g. by demethylation of its dimethyl ether or via standard coumarin-ring construction), and reviews note a large body of Chinese patents (on the order of ~90) covering daphnetin chemistry and applications ^{3Reference 3Hang S et al. · 2022Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic PotentialView study →}. Material for research is obtained by both plant extraction (Cortex Daphnes / Stellera) and synthesis.

Patents: not yet researched.

Toxicity & Safety

Daphnetin carries a [low] flag. It is a simple dihydroxycoumarin — not a furanocoumarin, so it does not photosensitise the skin the way psoralen/bergapten-type furocoumarins do, and it is not a 4-hydroxycoumarin/warfarin anticoagulant. Reviews describe a “promising safety profile,” but that judgement rests on animal studies, not human exposure, and no comprehensive isolate toxicology (repeat-dose, genotoxicity, reproductive) is established ^{1Reference 1Javed M et al. · 2022Daphnetin: A bioactive natural coumarin with diverse therapeutic potentialsView study →}.

Safety at a Glance

✅ Low / no toxicityDrug interactions

• Not phototoxic and not an anticoagulant. A plain dihydroxycoumarin — no furanocoumarin photosensitisation, no warfarin-type structure.
• Favourable in the models studied. Anti-arthritic and antimalarial rodent work reports tolerability at effective doses ^{4,7Reference 4Yao R et al. · 2011Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritisView study →Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →}.
• No human safety data. Every finding is in-vitro or animal; the “promising safety profile” is not a clinical clearance ^{1Reference 1Javed M et al. · 2022Daphnetin: A bioactive natural coumarin with diverse therapeutic potentialsView study →}.
• Plausible drug-interaction surface. As a catechol it is heavily conjugated, and a rat study shows co-administered herbs (licorice constituents) can raise its exposure ~1.5-fold — pharmacokinetic interactions are likely but uncharacterised in people ^{13Reference 13Zhang Y et al. · 2014AnimalThe effects of Glycyrrhizae uralensis and its major bioactive components on pharmacokinetics of daphnetin in Cortex daphnes in ratsView study →}.

Any pregnancy/lactation decision belongs to the specific herb or product a person might take (where intake is decided), not to this molecule page; no reproductive-safety dataset exists for the isolate.

Dosage

There is no established human dose for 7,8-dihydroxycoumarin (daphnetin) — it has never been administered to people as a defined isolate. The figures that appear in the literature are preclinical research doses, for example an antimalarial ED50 near 11 mg/kg and comparative dosing of 50–100 mg/kg in Plasmodium-infected mice ^{7,8Reference 7Yang YZ et al. · 1992In vitroDaphnetin: a novel antimalarial agent with in vitro and in vivo activityView study →Reference 8Wang QM et al. · 2004Comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasitesView study →}, and per-kilogram anti-arthritic doses in rats ^{4Reference 4Yao R et al. · 2011Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritisView study →}. These are research doses in animals and are not a personal recommendation.

References

1. Javed M, et al. (2022). Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/36249766/
2. Zhang L, et al. (2025). Investigating the Therapeutic Potential and Molecular Mechanisms of Daphnetin: A Comprehensive Review. Recent Patents on Anti-Cancer Drug Discovery. https://pubmed.ncbi.nlm.nih.gov/40237044/
3. Hang S, et al. (2022). Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic Potential. Chemistry & Biodiversity. https://pubmed.ncbi.nlm.nih.gov/35880614/
4. Yao R, et al. (2011). Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritis. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/21914445/
5. Tu L, et al. (2012). The therapeutic effects of daphnetin in collagen-induced arthritis involve its regulation of Th17 cells. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/22554834/
6. Shu K, et al. (2014). Therapeutic effect of daphnetin on the autoimmune arthritis through demethylation of proapoptotic genes in synovial cells. Journal of Translational Medicine. https://pubmed.ncbi.nlm.nih.gov/25311560/
7. Yang YZ, et al. (1992). Daphnetin: a novel antimalarial agent with in vitro and in vivo activity. The American Journal of Tropical Medicine and Hygiene. https://pubmed.ncbi.nlm.nih.gov/1311154/
8. Wang QM, et al. (2004). Comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasites. Biomedical and Environmental Sciences. https://pubmed.ncbi.nlm.nih.gov/15745243/
9. Yang EB, et al. (1999). Daphnetin, one of coumarin derivatives, is a protein kinase inhibitor. Biochemical and Biophysical Research Communications. https://pubmed.ncbi.nlm.nih.gov/10403826/
10. Yang J, et al. (2014). Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity. Molecules. https://pubmed.ncbi.nlm.nih.gov/25225718/
11. Yu W, et al. (2014). Daphnetin attenuates microglial activation and proinflammatory factor production via multiple signaling pathways. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/24747094/
12. Singh L, et al. (2021). Mechanistic interplay of various mediators involved in mediating the neuroprotective effect of daphnetin. Pharmacological Reports. https://pubmed.ncbi.nlm.nih.gov/33860917/
13. Zhang Y, et al. (2014). The effects of Glycyrrhizae uralensis and its major bioactive components on pharmacokinetics of daphnetin in Cortex daphnes in rats. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/24704595/
14. Han S, et al. (2020). Daphne giraldii Nitsche (Thymelaeaceae): Phytochemistry, pharmacology and medicinal uses. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/31901473/
15. Finn GJ, et al. (2004). Daphnetin induced differentiation of human renal carcinoma cells and its mediation by p38 mitogen-activated protein kinase. Biochemical Pharmacology. https://pubmed.ncbi.nlm.nih.gov/15081877/

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