Eupatorin

Eupatorin at a Glance

Eupatorin is a methoxylated flavone of java tea (Orthosiphon), chaste-tree, tansy and feverfew.

Its distinctive trait is that it behaves partly as a prodrug: CYP1 enzymes bioactivate it into more active metabolites — and because CYP1 enzymes are often upregulated in tumour tissue, that has been proposed as a route to selective activity, with the tumour performing its own activation.

Its research is preclinical.

What It's Used For

Eupatorin is a methoxylated flavone of the casticin/eupatilin/jaceosidin family, richest in java tea (Orthosiphon) and present in the flavonoid fractions of chaste-tree, tansy and feverfew. Its distinctive, honest hook is that it is partly a pro-drug: CYP1 enzymes (CYP1A1/1A2/1B1) bioactivate it by 4’-O-demethylation to cirsiliol and further-hydroxylated metabolites that are more cytotoxic than the parent, giving selective antiproliferative activity in CYP1-expressing cancer cells while sparing normal cells. That makes the anticancer story contingent on tissue CYP1 expression, not on dietary intake. All evidence is preclinical, and no human trial of the isolate exists.

CYP1-bioactivated, selective anticancer activity in vitro:submicromolar potency in CYP1-expressing breast lines with near-inactivity in normal cells, plus one mouse model ^{1,4,5Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →Reference 4Razak NA et al. · 2019Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 cells via cell-cycle arrest, anti-angiogenesis and apoptosisView study →Reference 5Abd Razak N et al. · 2020AnimalEupatorin suppressed tumour progression and enhanced immunity in a 4T1 murine breast-cancer modelView study →}.

The honest headline:almost entirely cell-line data (the single animal model is small), the effect is CYP1-contingent (not generalizable to systemic dietary intake), and there are no human trials ^{1,5Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →Reference 5Abd Razak N et al. · 2020AnimalEupatorin suppressed tumour progression and enhanced immunity in a 4T1 murine breast-cancer modelView study →}.

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. No human isolate data, so scores stay low by design.

The distinctive story: eupatorin is bioactivated by CYP1 enzymes to more cytotoxic metabolites, giving selective submicromolar potency in CYP1-expressing breast-cancer cells (MDA-MB-468) versus near-inactivity in normal MCF-10A cells ^{1,2Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →Reference 2Androutsopoulos VP et al. · 2009CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cellsView study →}.

Downstream it causes mitotic-checkpoint inactivation → polyploidy and G2/M arrest ^{3Reference 3Salmela AL et al. · 2012The flavonoid eupatorin inactivates the mitotic checkpoint, leading to polyploidy and apoptosisView study →}, caspase- and JNK-dependent, ROS-driven death in leukemia ^{6Reference 6Estévez S et al. · 2014Eupatorin-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathwayView study →}, and apoptosis/anti-angiogenesis in other breast lines ^{4Reference 4Razak NA et al. · 2019Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 cells via cell-cycle arrest, anti-angiogenesis and apoptosisView study →}.

One 4T1 mouse model reports tumor suppression with NF-κB downregulation ^{5Reference 5Abd Razak N et al. · 2020AnimalEupatorin suppressed tumour progression and enhanced immunity in a 4T1 murine breast-cancer modelView study →}.

Gap: almost entirely cell-line data, with a single small animal model, no human data, and an effect contingent on CYP1 expression — so “anticancer” cannot be generalized to systemic dietary intake ^{1,5Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →Reference 5Abd Razak N et al. · 2020AnimalEupatorin suppressed tumour progression and enhanced immunity in a 4T1 murine breast-cancer modelView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
CYP1A1/1A2/1B1	substrate → bioactivation to cirsiliol + hydroxylated metabolites (selective cytotoxicity in CYP1-high cells)	anticancer; also pharmacokinetics
Mitotic checkpoint / tubulin apparatus	checkpoint inactivation → polyploidy, G2/M arrest, apoptosis	anticancer
Caspase cascade + JNK/MAPK, ROS	caspase-dependent, JNK-required, ROS-driven apoptosis	anticancer (leukemia)
NF-κB / STAT1; iNOS, COX-2, NO	suppressed inflammatory gene expression	anti-inflammatory; anticancer (in vivo)
NO/cGMP, K⁺/Ca²⁺ channels (endothelium)	vasorelaxation	vasorelaxant / diuretic
Estrogen receptor	weak (flavonoid-fraction level)	historical chaste-tree context

Pharmacokinetics

No dedicated pharmacokinetic study exists. As a lipophilic trimethoxy-dihydroxyflavone, eupatorin follows the general flavone pattern — reasonable passive cell entry in vitro but poor expected oral bioavailability in vivo (intestinal/hepatic first-pass metabolism, glucuronidation/sulfation). The mechanistically important point is CYP1 metabolism: CYP1 enzymes convert eupatorin to more cytotoxic metabolites ^{1,2Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →Reference 2Androutsopoulos VP et al. · 2009CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cellsView study →}, so tissue CYP1 expression — not plasma parent concentration — likely governs activity, and CYP1A2 involvement raises theoretical drug-metabolism/interaction and chemoresistance considerations. In-vivo pharmacokinetics remain an open gap.

Clinical trials

There are no human trials of isolated eupatorin. Human exposure is only as a minor constituent of whole-plant preparations (chaste-tree extract; Orthosiphon stamineus/java tea), and all efficacy data are in-vitro or animal.

Completed	Planned	Terminated	Preclinical
—(none, isolate)	—	—	Moderate(in-vitro-dominant)

Last checked: July 2026.

Toxicity & Safety

Eupatorin has a long dietary history in java tea and related herbal preparations with no specific safety signal, and the real gap is that no dedicated toxicology exists for the isolated compound — its cytotoxicity in cell studies is selective for cancer cells, but that is a laboratory finding, not a safety clearance.

Safety at a Glance

Low / no toxicityDrug interactions

Long dietary and medicinal history. Consumed for generations in java tea and other herbal preparations with no specific safety signal.
Preclinical cytotoxicity is selective. It targets CYP1-expressing cancer cells, with normal cells markedly less affected.
Not recommended as an isolate in pregnancy or lactation. No reproductive data.
No dedicated isolate toxicology. No systemic toxicology, genotoxicity or repeat-dose study has been done.
CYP1A2 interaction is theoretical. Raised by its metabolism, not by any demonstrated harm.

Full Safety & Interactions Detail

Eupatorin has a low apparent toxicity — a dietary/medicinal methoxyflavone consumed for generations in java tea and other herbal preparations with no specific safety signal, and its preclinical cytotoxicity is selective for CYP1-expressing cancer cells, with normal cells markedly less affected ^{1,4Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →Reference 4Razak NA et al. · 2019Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 cells via cell-cycle arrest, anti-angiogenesis and apoptosisView study →}.

No dedicated systemic toxicology, genotoxicity or repeat-dose study exists for the isolate, and the CYP1A2 interaction point is theoretical rather than a demonstrated harm. Nor is there any reproductive or developmental data for isolated eupatorin — a gap that matters more than usual here, because the chaste-tree flavonoid fraction eupatorin belongs to carries a documented, if weak, estrogen-receptor interaction ^{11Reference 11Wuttke W et al. · 2003Chaste tree (Vitex agnus-castus) — pharmacology and clinical indicationsView study →}, and the molecule’s own antimitotic and pro-apoptotic activity is exactly the kind of mechanism reproductive toxicology exists to test for.

Dosage

There is no established human dose for isolated eupatorin, and none should be stated. Preclinical anchors only: in-vitro antiproliferative IC50 values are roughly submicromolar to low-micromolar in CYP1-expressing lines ^{1Reference 1Androutsopoulos V et al. · 2008Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolismView study →}, and the one in-vivo anticancer model used ~20 mg/kg in mice ^{5Reference 5Abd Razak N et al. · 2020AnimalEupatorin suppressed tumour progression and enhanced immunity in a 4T1 murine breast-cancer modelView study →} — research figures, not human guidance.

References

Androutsopoulos V, et al. (2008). Antiproliferative and cytostatic effects of eupatorin on MDA-MB-468 breast cancer cells due to CYP1-mediated metabolism. Breast Cancer Research. https://pubmed.ncbi.nlm.nih.gov/18454852/
Androutsopoulos VP, et al. (2009). CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells. Toxicology. https://pubmed.ncbi.nlm.nih.gov/19666078/
Salmela AL, et al. (2012). The flavonoid eupatorin inactivates the mitotic checkpoint, leading to polyploidy and apoptosis. Experimental Cell Research. https://pubmed.ncbi.nlm.nih.gov/22227008/
Razak NA, et al. (2019). Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 cells via cell-cycle arrest, anti-angiogenesis and apoptosis. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/30728391/
Abd Razak N, Yeap SK, Alitheen NB, et al. (2020). Eupatorin suppressed tumour progression and enhanced immunity in a 4T1 murine breast-cancer model. Integrative Cancer Therapies. https://pubmed.ncbi.nlm.nih.gov/32830560/
Estévez S, Marrero MT, Quintana J, et al. (2014). Eupatorin-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway. PLoS One. https://pubmed.ncbi.nlm.nih.gov/25390937/
Laavola M, et al. (2012). Flavonoids eupatorin and sinensetin from Orthosiphon stamineus inhibit inflammatory gene expression and STAT1 activation. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/22516932/
Lu J, Alarifi S, Ahamed A, et al. (2025). Eupatorin mitigates airway inflammation in ovalbumin-induced allergic asthma in mice by regulating Th2 cytokines. Journal of Biochemical and Molecular Toxicology. https://pubmed.ncbi.nlm.nih.gov/40127217/
Yam MF, et al. (2016). Mechanism of vasorelaxation induced by eupatorin in the rat aortic ring. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/27370961/
Yam MF, Tew WY, Tan CS, et al. (2024). Synergistic vasodilatory interaction of sinensetin, eupatorin and 3’-hydroxy-5,6,7,4’-tetramethoxyflavone. Hypertension Research. https://pubmed.ncbi.nlm.nih.gov/39300303/
Wuttke W, et al. (2003). Chaste tree (Vitex agnus-castus) — pharmacology and clinical indications. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/12809367/