The Sunlight Experiment

Compound Monograph

Scopoletin

Scopoletin (6-methoxy-7-hydroxycoumarin) is a widely distributed plant hydroxycoumarin. Its preclinical research centres on anti-inflammatory (NF-κB/Nrf2), antioxidant, and xanthine-oxidase-mediated urate-lowering activity — with no human trials of the isolate. It is not the hepatotoxic "coumarin" of fragrance nor a warfarin-type anticoagulant.

Work in progress

Classification

Scopoletin is a coumarin, part of the phenolics class. Antioxidant compounds built around one or more phenol rings — the flavonoids, tannins, phenolic acids, coumarins, and pigments behind much of a plant's protective chemistry.

Phenolics Coumarins

Where Does It Come From? (10)

Scopoletin is a naturally occurring coumarin, found in Stinging Nettle, Marshmallow, Passionflower and 7 other sources. It is well tolerated orally (low toxicity).

Cleavers Galium aparine Cramp Bark Dandelion Taraxacum officinale Marshmallow Althaea officinalis Mexican Tarragon Tagetes lucida NoniNoni — a marker compound Passionflower Passiflora incarnata Stevia Stevia rebaudiana Stinging Nettle Urtica dioica

Pharmacology & Research

Scopoletin (6-methoxy-7-hydroxycoumarin) is a hydroxycoumarin distributed widely but at trace levels across many medicinal plants — cleavers, Mexican tarragon, marshmallow, nettle and noni among them. It is worth naming its relatives at the outset, because they are separate molecules with separate pages: scopolin is its glucoside (a pro-drug form), scoparone the dimethyl analogue, umbelliferone the 7-hydroxycoumarin, and coumarin the simple parent — and none of those confusions should transfer their properties here (see Safety). Scopoletin’s own pharmacology is entirely preclinical (Tier B, no human trials of the isolate): its best-defined activities are anti-inflammatory NF-κB/Nrf2 signalling, direct antioxidant scavenging, and xanthine-oxidase inhibition with a uricosuric, urate-lowering effect 1,3Reference 12005Hypouricemic action of scopoletin arising from xanthine-oxidase inhibition and uricosuric activityView study →Reference 32022Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of scopoletinView study →.

What the evidence supports
  • A defined urate-lowering mechanism: scopoletin inhibits xanthine oxidase and promotes urate excretion, lowering uric acid in rodents 1Reference 12005Hypouricemic action of scopoletin arising from xanthine-oxidase inhibition and uricosuric activityView study → — its signature (preclinical) activity.
  • Reproducible anti-inflammatory/antioxidant signalling: NF-κB suppression plus Keap1–Nrf2/HO-1 induction across organ-injury models 3,5Reference 32022Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of scopoletinView study →Reference 52022AnimalAmeliorative impacts of scopoletin against vancomycin-induced intoxication in rats through Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK pathwaysView study →, and direct radical scavenging 2Reference 22003Antioxidant properties of scopoletin isolated from Sinomenium acutumView study →.
  • The honest headline: there are no human trials of isolated scopoletin, oral bioavailability is limited, and it is not the anticoagulant or hepatotoxic coumarin it is often confused with.
Evidence by indicationStrength of support
Anti-InflammatoryShaky
40%
Antioxidant / CytoprotectiveShaky
38%
Anti-Hyperuricemic / GoutShaky
36%
Neuroprotective / MAOShaky
24%
AntihypertensiveShaky
22%
AnticancerUnsupported
18%
1. Anti-inflammatory

Scopoletin suppresses NF-κB (IκBα–p65) signalling and pro-inflammatory cytokines while inducing the Keap1–Nrf2/HO-1 antioxidant response, shown in cerulein pancreatitis and lung injury 4Reference 42018AnimalProtective effect of scopoletin against cerulein-induced acute pancreatitis and associated lung injury in miceView study → and vancomycin nephro-intoxication models 5Reference 52022AnimalAmeliorative impacts of scopoletin against vancomycin-induced intoxication in rats through Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK pathwaysView study →, and reviewed across its targets 3Reference 32022Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of scopoletinView study →.

Gap: all animal and cell, with no isolated-compound human data and model-specific effect sizes 3,4Reference 32022Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of scopoletinView study →Reference 42018AnimalProtective effect of scopoletin against cerulein-induced acute pancreatitis and associated lung injury in miceView study →.

2. Antioxidant / cytoprotective

Scopoletin is a direct free-radical scavenger 2Reference 22003Antioxidant properties of scopoletin isolated from Sinomenium acutumView study → and protects hepatocytes against palmitate- and bile-acid-induced death by reducing ER and oxidative stress 8Reference 82022Scopoletin and umbelliferone protect hepatocytes against palmitate- and bile-acid-induced cell death by reducing ER stress and oxidative stressView study →.

Gap: foundational but non-specific chemistry shared by hydroxycoumarins, concentration-dependent, with no in-vivo human antioxidant readout 2Reference 22003Antioxidant properties of scopoletin isolated from Sinomenium acutumView study →. (Scopoletin also shows screening-level antimicrobial activity, e.g. isolated from Mexican tarragon 14Reference 14Céspedes CL et al. · 2006Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida)View study →, but only in vitro.)

3. Anti-hyperuricemic / gout

The signature scopoletin activity: it inhibits xanthine oxidase and adds a uricosuric action, lowering urate in a dedicated study 1Reference 12005Hypouricemic action of scopoletin arising from xanthine-oxidase inhibition and uricosuric activityView study →, with a micelle formulation reproducing the antihyperuricemic effect in hyperuricemic mice 7Reference 72020AnimalAntihyperuricemic efficacy of scopoletin-loaded Soluplus micelles in hyperuricemic miceView study →.

Gap: rodent only, with potency modest versus allopurinol/febuxostat and no clinical urate-lowering data — and the micelle requirement itself signals the free compound’s bioavailability limits 7Reference 72020AnimalAntihyperuricemic efficacy of scopoletin-loaded Soluplus micelles in hyperuricemic miceView study →.

4. Neuroprotective / MAO

Scopoletin modulates monoamine oxidase A/B and brain monoamine levels 9Reference 92016Effect of scopoletin on monoamine oxidases and brain aminesView study → and features among MAO-inhibitory coumarins 10Reference 102001Coumarins with monoamine-oxidase inhibitory activity and antioxidative coumarino-lignans from Hibiscus syriacusView study →; it reduced anxiety-like behaviour in an inflammatory-pain mouse model 6Reference 62020AnimalScopoletin ameliorates anxiety-like behaviours in a complete-Freund’s-adjuvant-induced mouse modelView study →, within a broader picture of coumarin antidepressant activity 11Reference 112023Antidepressant effects of coumarins and their derivatives: a critical analysis of research advancesView study →.

Gap: the behavioural antidepressant efficacy is mostly demonstrated for plant/coumarin fractions, not the purified isolate, and the MAO effects are moderate 9Reference 92016Effect of scopoletin on monoamine oxidases and brain aminesView study →.

5. Antihypertensive

Scopoletin produced acute and chronic antihypertensive effects in rats in a single plant-isolate study 12Reference 122019Acute and chronic antihypertensive effect of fractions, tiliroside and scopoletin from Malva parvifloraView study →.

Gap: one study, with the vasorelaxant mechanism inferred and not replicated for the isolate alone 12Reference 122019Acute and chronic antihypertensive effect of fractions, tiliroside and scopoletin from Malva parvifloraView study →.

6. Anticancer

Scopoletin shows pro-apoptotic and autophagy-activating signals in tumour cells 3Reference 32022Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of scopoletinView study →, though the strongest anticancer data are for synthetic 3-aryl-7-hydroxy scopoletin derivatives, not native scopoletin 13Reference 132022Design, synthesis and biological evaluation of 3-aryl-7-hydroxy scopoletin derivatives as autophagy activators against tumorigenesisView study →.

Gap: in-vitro-dominant and derivative-driven, with weak evidence for the parent compound 13Reference 132022Design, synthesis and biological evaluation of 3-aryl-7-hydroxy scopoletin derivatives as autophagy activators against tumorigenesisView study →.

Mechanisms

Target / pathwayEffectRelevant to
Xanthine oxidase (inhibition) + renal urate handling↓ urate production + ↑ excretionanti-hyperuricemia / gout
NF-κB (IκBα–p65)↓ pro-inflammatory cytokinesanti-inflammatory
Keap1–Nrf2 / HO-1↑ antioxidant/cytoprotective responseantioxidant, organ protection
Direct ROS/radical scavenging↓ oxidative stressantioxidant
Monoamine oxidase A/B (modulation)↑ brain monoaminesneuro / antidepressant

Pharmacokinetics

Load-bearing and honestly limited. Scopoletin is a small hydroxy-methoxycoumarin with moderate-to-poor oral bioavailability — rapidly absorbed but extensively metabolised by phase-II conjugation (glucuronidation/sulfation, the coumarin-class pattern), giving short systemic exposure. Its glucoside scopolin is hydrolysed to scopoletin in vivo, and both are cleared rapidly and excreted in urine 15Reference 152019AnimalEvaluation of the pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in rats by LC-MS/MSView study →; elimination from a standardised plant fraction likewise shows fast clearance 16Reference 162020Elimination pharmacokinetics of a scopoletin-containing standardised fraction of Sphaeralcea angustifolia administered orallyView study →, and metabolite profiling documents the coumarin phase-I/II routes 17Reference 172020Metabolic profiling of coumarins by UPLC-MS-based metabolomics and multiple mass-defect filterView study →. The fact that a micelle formulation was needed to achieve an antihyperuricemic effect in vivo 7Reference 72020AnimalAntihyperuricemic efficacy of scopoletin-loaded Soluplus micelles in hyperuricemic miceView study → independently confirms real bioavailability constraints — this is not a well-absorbed oral agent.

Clinical trials

There are no human trials of the isolated molecule for any indication. Human exposure occurs only via whole plants and products (noni juice, nettle, marshmallow), where scopoletin is one of many constituents and its individual contribution is not isolated — so any “clinical” framing belongs to the plant product, not the compound.

CompletedPlannedTerminatedPreclinical
—(isolate); plant-product only——Extensive

Last checked: July 2026.

Toxicity & Safety

Scopoletin has a low-toxicity preclinical profile — it behaves as a protective/antioxidant agent in the organ-injury models above rather than a toxicant, and it occurs at trace levels in foods and common herbs. One class clarification corrects a frequent error: scopoletin is a 6-methoxy-7-hydroxycoumarin, and it is not the simple parent “coumarin” of fragrance chemistry (associated with dose-dependent hepatotoxicity), nor a 4-hydroxycoumarin/warfarin-type anticoagulant — vitamin-K-antagonist anticoagulation belongs to the synthetic dicoumarol/warfarin subclass, not to simple hydroxymethoxycoumarins. So the common “coumarins interact with blood thinners” caution overstates the risk here and should be treated as theoretical and unproven rather than a class-wide warning. Genuine interactions are only theoretical: possible additive xanthine-oxidase effects with urate-lowering drugs, and MAO modulation as a plausibility flag not demonstrated at dietary exposure.

Pregnancy & lactation

Insufficient data — avoid concentrated/supplemental use. No reproductive-toxicology studies of the isolate exist; trace dietary amounts in whole herbs are not a specific concern, but isolated or high-dose scopoletin cannot be considered established as safe in pregnancy or lactation.

Dosage

There is no established human dose, and nothing here is a recommendation. Preclinical models used oral rodent doses of roughly 1–50 mg/kg/day across the anti-inflammatory, antioxidant, antihypertensive and antihyperuricemic studies, with in-vitro work at low-micromolar concentrations — figures that do not translate to a human dose, and which the bioavailability limits above make an inefficient basis for free-compound oral dosing.

References

  1. (2005). Hypouricemic action of scopoletin arising from xanthine-oxidase inhibition and uricosuric activity. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/15729630/
  2. (2003). Antioxidant properties of scopoletin isolated from Sinomenium acutum. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/12916088/
  3. (2022). Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of scopoletin. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33847360/
  4. (2018). Protective effect of scopoletin against cerulein-induced acute pancreatitis and associated lung injury in mice. Pancreas. https://pubmed.ncbi.nlm.nih.gov/29595543/
  5. (2022). Ameliorative impacts of scopoletin against vancomycin-induced intoxication in rats through Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK pathways. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/34848155/
  6. (2020). Scopoletin ameliorates anxiety-like behaviours in a complete-Freund’s-adjuvant-induced mouse model. Molecular Brain. https://pubmed.ncbi.nlm.nih.gov/32019580/
  7. (2020). Antihyperuricemic efficacy of scopoletin-loaded Soluplus micelles in hyperuricemic mice. Drug Development and Industrial Pharmacy. https://pubmed.ncbi.nlm.nih.gov/32811191/
  8. (2022). Scopoletin and umbelliferone protect hepatocytes against palmitate- and bile-acid-induced cell death by reducing ER stress and oxidative stress. Toxicology and Applied Pharmacology. https://pubmed.ncbi.nlm.nih.gov/34979142/
  9. (2016). Effect of scopoletin on monoamine oxidases and brain amines. Neurochemistry International. https://pubmed.ncbi.nlm.nih.gov/26796202/
  10. (2001). Coumarins with monoamine-oxidase inhibitory activity and antioxidative coumarino-lignans from Hibiscus syriacus. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/11575966/
  11. (2023). Antidepressant effects of coumarins and their derivatives: a critical analysis of research advances. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/37543158/
  12. (2019). Acute and chronic antihypertensive effect of fractions, tiliroside and scopoletin from Malva parviflora. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/30606987/
  13. (2022). Design, synthesis and biological evaluation of 3-aryl-7-hydroxy scopoletin derivatives as autophagy activators against tumorigenesis. European Journal of Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/36242987/
  14. Céspedes CL, et al. (2006). Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida). Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/19127719/
  15. (2019). Evaluation of the pharmacokinetics, bioavailability and urinary excretion of scopolin and its metabolite scopoletin in rats by LC-MS/MS. Biomedical Chromatography. https://pubmed.ncbi.nlm.nih.gov/31412148/
  16. (2020). Elimination pharmacokinetics of a scopoletin-containing standardised fraction of Sphaeralcea angustifolia administered orally. Journal of Pharmaceutical and Biomedical Analysis. https://pubmed.ncbi.nlm.nih.gov/32045824/
  17. (2020). Metabolic profiling of coumarins by UPLC-MS-based metabolomics and multiple mass-defect filter. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/32174209/