Esculetin

Esculetin at a Glance

Esculetin (6,7-dihydroxycoumarin) is a catechol-type coumarin found in chicory, Mexican tarragon and ash bark — the aglycone released from esculin.

Its preclinical research centres on antioxidant and Nrf2 activity, anti-inflammatory effects and lipoxygenase inhibition, the last giving it a defined mechanism rather than a general antioxidant claim.

Note that despite being a coumarin it is not an anticoagulant — that property belongs to the 4-hydroxycoumarin dicoumarol, a structurally different molecule.

Esculetin & Esculin: What the Sugar Changes

Esculin is esculetin carrying a glucose at the 6-position. Everything else about the two molecules is identical, and almost everything that matters about them is different.

Absorption. The glucoside is the poorly absorbed one. Dietary esculin has to be cleaved by gut-microbial β-glucosidase before appreciable absorption, which makes esculetin the moiety that actually reaches tissue and, for much of esculin’s in-vivo activity, the effector ^{4,13Reference 4Ju S et al. · 2024ReviewAntioxidant and anti-inflammatory effects of esculin and esculetin — reviewView study →Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →}. That conversion is not guaranteed: β-glucosidase activity and the ability to ferment plant glucosides vary by bacterial species and even by strain across Bifidobacterium ^{17Reference 17Modrackova N et al. · 2020In vitroBifidobacterium β-Glucosidase Activity and Fermentation of Dietary Plant Glucosides Is Species and Strain Specific — in vitroView study →}, so how much esculetin a person gets from a given dose of esculin depends on their gut flora.

One experiment measures the gap directly. Beagle dogs given a single oral dose of a plant extract containing all four ash-bark coumarins reached peak plasma concentrations of 209.9 ng/mL of esculetin against 46.75 ng/mL of esculin, and 369.7 ng/mL of fraxetin against 67.04 ng/mL of fraxin — the two aglycones four to five times higher than their own glucosides, in the same animals, from the same dose ^{21Reference 21Wang Z et al. · 2018Simultaneous Determination of Aesculin, Aesculetin, Fraxetin, Fraxin and Polydatin in Beagle Dog Plasma by UPLC-ESI-MS/MS and Its Application in a Pharmacokinetic Study after Oral Administration Extracts of Ledum palustre L. — animal pharmacokinetic modelView study →}. Esculin also peaked latest of the four (1.32 h), which is what a molecule that has to wait for bacterial cleavage looks like.

Potency and target. The free catechol — the 6,7-dihydroxy pair the glucose was covering — is what makes esculetin a stronger direct radical scavenger than mono-hydroxy coumarins, and it is required for the 5-lipoxygenase inhibition that is esculetin’s signature ^{5,6Reference 5Neichi T et al. · 1983In vitroInhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis — in vitroView study →Reference 6Sekiya K et al. · 1982In vitroSelective inhibition of platelet lipoxygenase by esculetin — in vitroView study →}.

But the sugar is not simply a mask. Aesculin only marginally activates Nrf2 on its own; adding a further glucose to make 3-O-β-D-glycosyl aesculin produced robust Nrf2 activation, suppressed neutrophilic lung inflammation in mice, and improved survival in a sepsis model — none of which the parent aesculin did, and none of which happened in Nrf2-knockout mice ^{15Reference 15Kim KH et al. · 2016In vitroGlycosylation enables aesculin to activate Nrf2 — in vitro and mouse modelView study →}. Glycosylation altered the molecule’s function rather than merely reducing it.

Toxicity runs the other way from potency. Esculin is the named toxic principle behind raw horse chestnut and is removed during the manufacture of standardised extract; esculetin is not, and is widely distributed in edible plants. The aglycone is the more pharmacologically active of the two and the less alarming.

Not Warfarin, Not “Coumarin”

Two things get attached to any molecule with “coumarin” in its name, and neither applies here.

It is not a blood thinner. Warfarin’s anticoagulant mechanism belongs to 4-hydroxycoumarins — dicoumarol and its synthetic descendants — which act by inhibiting vitamin K epoxide reductase. Esculetin is a 6,7-dihydroxycoumarin: the hydroxyls are on the benzene ring, not at C-4, and the vitamin-K mechanism is not available to it. The same discipline applies to esculin, fraxin and scopoletin.

There is one genuine, and different, blood-related caveat: esculetin inhibits platelet lipoxygenase ^{6Reference 6Sekiya K et al. · 1982In vitroSelective inhibition of platelet lipoxygenase by esculetin — in vitroView study →}. That is an eicosanoid mechanism, not anticoagulation, and it is the honest basis for a theoretical additive caution alongside antiplatelet drugs — not for calling esculetin a coumarin anticoagulant.

It is not the hepatotoxic fragrance “coumarin” either. That is the unsubstituted parent molecule, the one with the new-mown-hay smell that is restricted in food. Esculetin is a different, hydroxylated compound with a different metabolic fate.

What It's Used For

Esculetin (aesculetin, 6,7-dihydroxycoumarin) is the aglycone of esculin — esculin is esculetin 6-O-glucoside, and gut β-glucosidase releases esculetin as the better-absorbed, generally active moiety, so esculetin is the effector of much of esculin’s in-vivo activity. Its ortho-dihydroxy (catechol) arrangement makes it a stronger intrinsic antioxidant than the mono-hydroxy coumarins, and its most distinctive mechanism is a historic one: it is a classic inhibitor of 5-lipoxygenase. Two discipline points (as for scopoletin): it is a 6,7-dihydroxycoumarin, not a 4-hydroxycoumarin/warfarin-type anticoagulant, and it is not the hepatotoxic fragrance “coumarin.” All evidence is preclinical.

Evidence by IndicationStrength of support · Beta

01Antioxidant / Nrf2Shaky40%Catechol scavenging + Nrf2/HO-1 induction ^{2,3,4,14Reference 2Garg SS et al. · 2022ReviewPharmacological and Therapeutic Applications of Esculetin — reviewView study →Reference 3Jayakumar T et al. · 2022In vitroActivation of Nrf2 by Esculetin Mitigates Inflammatory Responses through Suppression of NF-κB Signaling Cascade in RAW 264.7 Cells — in vitroView study →Reference 4Ju S et al. · 2024ReviewAntioxidant and anti-inflammatory effects of esculin and esculetin — reviewView study →Reference 14Zhang Z et al. · 2024AnimalEsculetin attenuates cerebral ischemia-reperfusion injury and protects neurons through Nrf2 activation in rats — rat in vivo animal modelView study →}

02Anti-inflammatory & 5-lipoxygenaseShaky38%NF-κB suppression + classic 5-LOX inhibition ^{3,5,6Reference 3Jayakumar T et al. · 2022In vitroActivation of Nrf2 by Esculetin Mitigates Inflammatory Responses through Suppression of NF-κB Signaling Cascade in RAW 264.7 Cells — in vitroView study →Reference 5Neichi T et al. · 1983In vitroInhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis — in vitroView study →Reference 6Sekiya K et al. · 1982In vitroSelective inhibition of platelet lipoxygenase by esculetin — in vitroView study →}

03AnticancerShaky32%Apoptosis across tumor cell lines ^{1,7,8,9Reference 1Liu M et al. · 2024ReviewTherapeutic potential of esculetin in various cancer types — reviewView study →Reference 7Chu CY et al. · 2001In vitroInduction of apoptosis by esculetin in human leukemia cells — in vitroView study →Reference 8Arora R et al. · 2016In vitroEsculetin induces antiproliferative and apoptotic response in pancreatic cancer cells by directly binding to KEAP1 — in vitroView study →Reference 9Kim AD et al. · 2015In vitroEsculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress — in vitroView study →}

04AntidiabeticShaky26%Streptozotocin-diabetic rat studies ^{10Reference 10Prabakaran D · 2013AnimalProtective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats — rat in vivo animal modelView study →}

05HepatoprotectiveShaky24%NAFLD and hepatotoxin rat models ^{11,12Reference 11Pandey A et al. · 2017AnimalEsculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway — animal modelView study →Reference 12Tien YC et al. · 2011AnimalEsculetin ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats — rat in vivo animal modelView study →}

Mechanisms

Pharmacokinetics

Esculetin’s pharmacokinetics have been measured directly, which is more than most plant coumarins can say. Rats given 10 mg/kg orally or intravenously showed a mean oral bioavailability of 19%, a half-life of 2.08 ± 0.46 hours, a steady-state volume of distribution of 1.81 ± 0.52 L/kg and clearance of 1.27 ± 0.26 L/h/kg ^{13Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →}. Nineteen percent is low but not negligible — and it is a real number, which matters more than the qualitative “poorly bioavailable” that circulates for most molecules in this class.

What limits it is phase-II conjugation, chiefly glucuronidation at the C-7 hydroxyl, so free esculetin in plasma is brief and much of what circulates is conjugated ^{13Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →}. That is the standard fate of a catechol, and it is the caveat under every in-vitro result for this molecule: the concentrations that inhibit 5-lipoxygenase or bind KEAP1 in a dish are free-drug concentrations, and free drug is the fraction that disappears fastest.

There is also a loop back to the glucoside. Esculin absorbs poorly until gut bacteria cleave it, at which point it becomes esculetin — so a dose of esculin is a slow, distal, flora-dependent way of delivering the same molecule ^{4,13,17Reference 4Ju S et al. · 2024ReviewAntioxidant and anti-inflammatory effects of esculin and esculetin — reviewView study →Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →Reference 17Modrackova N et al. · 2020In vitroBifidobacterium β-Glucosidase Activity and Fermentation of Dietary Plant Glucosides Is Species and Strain Specific — in vitroView study →}, and it reaches roughly a fifth of the plasma concentration esculetin does from the same extract ^{21Reference 21Wang Z et al. · 2018Simultaneous Determination of Aesculin, Aesculetin, Fraxetin, Fraxin and Polydatin in Beagle Dog Plasma by UPLC-ESI-MS/MS and Its Application in a Pharmacokinetic Study after Oral Administration Extracts of Ledum palustre L. — animal pharmacokinetic modelView study →}. No human pharmacokinetic study of either exists.

Clinical Trials

There are no human clinical trials of isolated esculetin for any indication; all pharmacology is preclinical.

Last checked: September 2026.

Isolate vs. Plant Studies

Nearly all of it is isolate work, and it is clean isolate work — the 5-lipoxygenase inhibition, the KEAP1 binding, the apoptosis assays and the rodent diabetes and liver models all used purified esculetin at stated doses ^{5,8,10,11Reference 5Neichi T et al. · 1983In vitroInhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis — in vitroView study →Reference 8Arora R et al. · 2016In vitroEsculetin induces antiproliferative and apoptotic response in pancreatic cancer cells by directly binding to KEAP1 — in vitroView study →Reference 10Prabakaran D · 2013AnimalProtective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats — rat in vivo animal modelView study →Reference 11Pandey A et al. · 2017AnimalEsculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway — animal modelView study →}. The pharmacokinetics were measured on the pure compound too ^{13Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →}. What that buys is a molecule whose activity is properly attributed; what it does not buy is any evidence that a plant containing esculetin does the same thing.

The plant-side evidence is thin and points at mixtures. In Mexican tarragon the coumarins — esculetin alongside 7,8-dihydroxycoumarin and 6-hydroxy-7-methoxycoumarin — were isolated from aerial parts and tested as an antimicrobial panel, so the activity belongs to a set of related molecules, not to esculetin alone ^{16Reference 16Céspedes CL et al. · 2006In vitroAntifungal and antibacterial activities of Mexican tarragon (Tagetes lucida) — in vitroView study →}. In cramp bark and chicory, esculetin is a minor constituent among tannins, flavonoids and other coumarins, and no study attributes those herbs’ effects to it.

The one place the isolate/plant question genuinely resolves is the esculin loop: because gut bacteria convert esculin to esculetin, a plant that supplies esculin is, functionally, supplying esculetin at one remove ^{4,17Reference 4Ju S et al. · 2024ReviewAntioxidant and anti-inflammatory effects of esculin and esculetin — reviewView study →Reference 17Modrackova N et al. · 2020In vitroBifidobacterium β-Glucosidase Activity and Fermentation of Dietary Plant Glucosides Is Species and Strain Specific — in vitroView study →}. That is a real transfer mechanism rather than an assumption — but the amount transferred depends on the individual’s gut flora and has never been measured in a person.

Its Role in Plants

Esculetin is a 6,7-dihydroxycoumarin built from the phenylpropanoid pathway — p-coumaric acid is hydroxylated and lactonised to umbelliferone, then hydroxylated again at C-6 to give the catechol. Plants rarely store it in that free form. They glucosylate it, mostly at the 6-position, to give esculin, which is water-soluble, less chemically reactive, and safe to accumulate in the vacuole — the same storage logic that governs most plant phenolics.

Two functions are well described for the pair. The first is defence: coumarins of this type are antimicrobial, and the Mexican tarragon coumarin fraction that contains esculetin is active against fungi and bacteria ^{16Reference 16Céspedes CL et al. · 2006In vitroAntifungal and antibacterial activities of Mexican tarragon (Tagetes lucida) — in vitroView study →}. The second is light management — esculin fluoresces strongly blue, and horse-chestnut bark infusions are one of the classic natural fluorescent solutions, a property that made them a nineteenth-century laboratory curiosity and later a diagnostic reagent (see esculin).

In Fraxinus bark, esculetin sits in a small family of related coumarins — with esculin, fraxetin and fraxin — that differ only in which hydroxyls are methylated or glucosylated. It is a good illustration of how a plant makes a chemical series rather than a compound.

Prevalence in Nature

Esculetin is widely distributed and almost always minor. It appears across the Oleaceae, Asteraceae, Sapindaceae and Euphorbiaceae, usually in bark or aerial parts, and usually alongside its own glucoside and one or two methylated relatives rather than on its own.

The best-documented sources are ash bark (Fraxinus spp.), where it occurs with esculin, fraxetin and fraxin; chicory (Cichorium intybus); Mexican tarragon (Tagetes lucida) aerial parts, where it was isolated with two other dihydroxy/methoxy coumarins ^{16Reference 16Céspedes CL et al. · 2006In vitroAntifungal and antibacterial activities of Mexican tarragon (Tagetes lucida) — in vitroView study →}; cramp bark (Viburnum opulus), where it is the second coumarin after scopoletin; and Artemisia capillaris. The rat pharmacokinetic work describes it as the main active constituent isolated from Artemisia montana and Euphorbia lathyris ^{13Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →}. Horse chestnut (Aesculus spp.) carries it in the form of its glucoside esculin rather than free.

Quantified content figures are largely absent from the accessible literature for every one of these, so the table below records source and part rather than concentration.

Major Natural Sources

Source	Family	Part	Form
Ash (Fraxinus spp.)	Oleaceae	Bark	Free and as esculin; with fraxetin and fraxin
Horse chestnut (Aesculus spp.)	Sapindaceae	Bark, seed	Almost entirely as esculin, the glucoside
Chicory (Cichorium intybus)	Asteraceae	Root, aerial	Free, minor
Mexican tarragon (Tagetes lucida)	Asteraceae	Aerial parts	Free, with two related coumarins 16Reference 16Céspedes CL et al. · 2006In vitroAntifungal and antibacterial activities of Mexican tarragon (Tagetes lucida) — in vitroView study →
Cramp bark (Viburnum opulus)	Adoxaceae	Bark	Free, minor; second coumarin after scopoletin
Artemisia capillaris, A. montana	Asteraceae	Aerial	Described as a main active constituent 13Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →
Euphorbia lathyris	Euphorbiaceae	—	Described as a main active constituent 13Reference 13Kwak JH et al. · 2021AnimalOral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal modelView study →

Discovery & Synthesis

Esculetin came out of the horse chestnut, and it arrived as a degradation product rather than a discovery in its own right. Friedrich Rochleder worked through the crystallised constituents of Aesculus hippocastanum in the early 1860s ^{20Reference 20Rochleder F · 1863Ueber die krystallisirten Bestandtheile der Rosskastanie (Aesculus Hippocastanum L.)View study →}; the glucoside esculin — named for the tree — was the substance the chemistry of that period was chasing, and esculetin (“aesculetin”) is what is left when the sugar is hydrolysed off. Hugo Schiff spent the 1870s and 1880s establishing esculin’s constitution and preparing acetyl derivatives of both the glucoside and the aglycone, which is where the pair’s structural relationship was settled ^{18Reference 18Schiff H · 1880Ueber Acetylderivate des Aesculins und AesculetinsView study →}.

The first synthesis was 1899, when Ludwig Gattermann and M. Köbner made both daphnetin and aesculetin — placing esculetin among the earliest coumarins ever synthesised, roughly a decade after Pechmann’s condensation made simple coumarins reachable at all ^{19Reference 19Gattermann L · 1899Synthese des Daphnetins und AesculetinsView study →}.

Manufacture today is hydrolysis, not synthesis. Commercial esculetin is obtained by cleaving the glucose from esculin, which is itself extracted from horse-chestnut or ash bark — the same operation Rochleder’s contemporaries performed, at scale. It is a research chemical: there is no licensed drug and no supplement product, so demand is small.

Patents: not yet researched.

Toxicity & Safety

Esculetin is a coumarin that does not carry the two reputations coumarins usually attract — it is neither a warfarin-type blood thinner nor the hepatotoxic fragrance “coumarin,” and unlike its glucoside esculin it is not a named plant poison.

Safety at a Glance

✅ Low / no toxicityDrug interactions

• Not a blood thinner. A 6,7-dihydroxycoumarin, not a 4-hydroxycoumarin — warfarin’s mechanism does not apply, and neither does the hepatotoxic fragrance “coumarin.”
• Widely distributed in edible plants. Dosed orally at ~10–40 mg/kg in rodents without reported lethality.
• No safety study of the isolate exists. No repeat-dose, genotoxicity or reproductive data, and no human exposure at all.
• Avoid in pregnancy and lactation. No reproductive data and no human exposure data at all.
• Theoretical additive antiplatelet caution. It inhibits platelet and leukocyte lipoxygenase, so take care alongside antiplatelet drugs.

Full Safety & Interactions Detail

Esculetin sits a step below esculin on caution, and the reason is specific rather than a matter of degree: esculin is the named toxic principle behind raw horse chestnut and the compound removed during the manufacture of standardised extract, and esculetin is not. Esculetin is widely distributed in edible plants and has been dosed orally at ~10–40 mg/kg in rodents without reported lethality ^{10,11Reference 10Prabakaran D · 2013AnimalProtective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats — rat in vivo animal modelView study →Reference 11Pandey A et al. · 2017AnimalEsculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway — animal modelView study →}.

The class disclaimers are handled above — it is not a warfarin-type anticoagulant and not the hepatotoxic fragrance “coumarin.”

The one honest interaction caveat is the lipoxygenase one. Esculetin inhibits platelet and leukocyte lipoxygenase ^{6Reference 6Sekiya K et al. · 1982In vitroSelective inhibition of platelet lipoxygenase by esculetin — in vitroView study →}, which is an eicosanoid mechanism rather than anticoagulation, but it is enough to warrant a theoretical additive caution alongside antiplatelet drugs.

What has not been assessed. No repeat-dose toxicology, genotoxicity package or reproductive study exists for isolated esculetin, and no person has taken it. The absence of reported harm reflects the absence of study, not a clean safety record.

Dosage

There is no established human dose — esculetin has never been given to a person as an isolate, and it is not sold as a supplement. The figures below are the exposures used in the research described above.

Herbal exposure is indirect and unquantified: esculetin is a minor constituent of the plants that carry it, and much of what reaches tissue from a plant arrives as esculin and is converted by gut bacteria at a rate nobody has measured in a person ^{17Reference 17Modrackova N et al. · 2020In vitroBifidobacterium β-Glucosidase Activity and Fermentation of Dietary Plant Glucosides Is Species and Strain Specific — in vitroView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Liu M, Sheng Y, Guo F, et al. (2024). Therapeutic potential of esculetin in various cancer types — review. Oncology Letters. https://pubmed.ncbi.nlm.nih.gov/38774454/
2. Garg SS, Gupta J, Sahu D, et al. (2022). Pharmacological and Therapeutic Applications of Esculetin — review. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/36293500/
3. Jayakumar T, Huang CJ, Yen TL, et al. (2022). Activation of Nrf2 by Esculetin Mitigates Inflammatory Responses through Suppression of NF-κB Signaling Cascade in RAW 264.7 Cells — in vitro. Molecules. https://pubmed.ncbi.nlm.nih.gov/36014382/
4. Ju S, Tan Y, Wang Q, et al. (2024). Antioxidant and anti-inflammatory effects of esculin and esculetin — review. Experimental and Therapeutic Medicine. https://pubmed.ncbi.nlm.nih.gov/38682114/
5. Neichi T, Koshihara Y, Murota S (1983). Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis — in vitro. Biochimica et Biophysica Acta. https://pubmed.ncbi.nlm.nih.gov/6411127/
6. Sekiya K, Okuda H, Arichi S (1982). Selective inhibition of platelet lipoxygenase by esculetin — in vitro. Biochimica et Biophysica Acta. https://pubmed.ncbi.nlm.nih.gov/6814494/
7. Chu CY, Tsai YY, Wang CJ, et al. (2001). Induction of apoptosis by esculetin in human leukemia cells — in vitro. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/11282109/
8. Arora R, Sawney S, Saini V, et al. (2016). Esculetin induces antiproliferative and apoptotic response in pancreatic cancer cells by directly binding to KEAP1 — in vitro. Molecular Cancer. https://pubmed.ncbi.nlm.nih.gov/27756327/
9. Kim AD, Madduma Hewage SR, Piao MJ, et al. (2015). Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress — in vitro. Cell Biochemistry and Function. https://pubmed.ncbi.nlm.nih.gov/26439795/
10. Prabakaran D, Ashokkumar N (2013). Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats — rat in vivo animal model. Biochimie. https://pubmed.ncbi.nlm.nih.gov/23079336/
11. Pandey A, Raj P, Goru SK, et al. (2017). Esculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway — animal model. Pharmacological Reports. https://pubmed.ncbi.nlm.nih.gov/28527877/
12. Tien YC, Liao JC, Chiu CS, et al. (2011). Esculetin ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats — rat in vivo animal model. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/21747724/
13. Kwak JH, Kim Y, Staatz CE, et al. (2021). Oral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats — rat pharmacokinetic animal model. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/33949288/
14. Zhang Z, Zhang J, Shi R, et al. (2024). Esculetin attenuates cerebral ischemia-reperfusion injury and protects neurons through Nrf2 activation in rats — rat in vivo animal model. Brazilian Journal of Medical and Biological Research. https://pubmed.ncbi.nlm.nih.gov/39504067/
15. Kim KH, Park H, Park HJ, et al. (2016). Glycosylation enables aesculin to activate Nrf2 — in vitro and mouse model. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/27417293/
16. Céspedes CL, Avila JG, Martínez A, et al. (2006). Antifungal and antibacterial activities of Mexican tarragon (Tagetes lucida) — in vitro. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/19127719/
17. Modrackova N, Vlkova E, Tejnecky V, et al. (2020). Bifidobacterium β-Glucosidase Activity and Fermentation of Dietary Plant Glucosides Is Species and Strain Specific — in vitro. Microorganisms. https://pubmed.ncbi.nlm.nih.gov/32503148/
18. Schiff H (1880). Ueber Acetylderivate des Aesculins und Aesculetins. Berichte der deutschen chemischen Gesellschaft. https://doi.org/10.1002/cber.188001302171
19. Gattermann L, Köbner M (1899). Synthese des Daphnetins und Aesculetins. Berichte der deutschen chemischen Gesellschaft. https://doi.org/10.1002/cber.18990320146
20. Rochleder F (1863). Ueber die krystallisirten Bestandtheile der Rosskastanie (Aesculus Hippocastanum L.). Journal für Praktische Chemie. https://doi.org/10.1002/prac.18630900163
21. Wang Z, Zhu W, Liu H, et al. (2018). Simultaneous Determination of Aesculin, Aesculetin, Fraxetin, Fraxin and Polydatin in Beagle Dog Plasma by UPLC-ESI-MS/MS and Its Application in a Pharmacokinetic Study after Oral Administration Extracts of Ledum palustre L. — animal pharmacokinetic model. Molecules. https://pubmed.ncbi.nlm.nih.gov/30205426/

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