Leucodin

Leucodin at a Glance

Leucodin is a guaianolide sesquiterpene lactone — one of the bitter, tricyclic terpenoids that characterise the daisy family (Asteraceae). Its proper chemical synonym is desacetoxymatricarin, and it is also spelled leucodine or leukodin ^{12,15Reference 12Tschiggerl C · 2012Guaianolides and volatile compounds in chamomile tea — [phytochemical analysis]View study →Reference 15Martinez VM et al. · 1988Conformational analysis of achillin and leukodin — [structural chemistry]View study →}.

It is best known from yarrow (Achillea millefolium), where bioassay-guided fractionation of the flower hexane extract yielded leucodin and its C-11 epimer achillin as the two major components — and identified them as the molecules responsible for the extract’s blood-pressure-lowering and smooth-muscle-relaxant activity in rats ^{1,2Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →Reference 2Arias-Durán L et al. · 2020AnimalTracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds — [rat ex vivo]View study →}. That is the clearest thing this molecule does, and it is entirely animal-level.

Two things make leucodin worth a careful page rather than a quick one. First, its name sits in a genuinely confused cluster — leucodin, achillin, matricarin, desacetylmatricarin and dehydroleucodin are five different molecules that are routinely conflated, and the confusion changes what you can attribute to which. Second, leucodin lacks the α-methylene-γ-lactone group that drives most of the sesquiterpene-lactone class’s pharmacology and toxicology — so the usual class claims about thiol alkylation and NF-κB do not transfer to it, and there is published experimental evidence that they don’t ^{8Reference 8Giordano OS et al. · 1990AnimalThe gastric cytoprotective effect of several sesquiterpene lactones — [rat in vivo]View study →}.

Leucodin, Achillin & Matricarin — Untangling The Names

Leucodin is not desacetylmatricarin. This is the single most important thing to get right about this molecule, because a great deal of secondary writing treats the two as synonyms. They are different compounds with different molecular formulas ^{22Reference 22PubChem compound records — Leucodin (CID et al.https://pubchem.ncbi.nlm.nih.gov/compound/167683View study →}:

Compound	Formula	MW	PubChem CID	Relationship
Leucodin (desacetoxymatricarin)	C₁₅H₁₈O₃	246.3	167683	The molecule here — no oxygen at C-8
Achillin	C₁₅H₁₈O₃	246.3	442139	C-11 epimer of leucodin — same connectivity, inverted methyl
Desacetylmatricarin (deacetylmatricarin, austricin)	C₁₅H₁₈O₄	262.3	6713966	Matricarin minus its acetyl — keeps an 8-hydroxyl
Matricarin	C₁₇H₂₀O₅	304.3	3083923	The 8-O-acetyl ester of desacetylmatricarin
Dehydroleucodin	C₁₅H₁₆O₃	244.3	73440	Leucodin plus an exocyclic methylene at C-11/C-13

The prefix is the tell: desacetoxymatricarin (= leucodin) has lost the whole acetoxy group and carries no oxygen at C-8; desacetylmatricarin has lost only the acetyl and retains the hydroxyl. One letter, one oxygen atom, two molecules.

This is not a pedantic distinction. Phytochemists routinely isolate leucodin and desacetylmatricarin from the same plant in the same run — from a Hungarian Achillea millefolium taxon ^{11Reference 11Glasl S et al. · 2002Sesquiterpenes and flavonoid aglycones from a Hungarian taxon of the Achillea millefolium group — [phytochemical isolation]View study →}, from basin big sagebrush ^{7Reference 7Anibogwu R et al. · 2024In vitroSesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]View study →}, and in the analytical methods developed specifically to tell the five guaianolides apart by TLC and HPLC ^{10Reference 10Glasl S et al. · 2003TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]View study →}. And where the two have been assayed head-to-head, they behave differently: against mast-cell degranulation, desacetylmatricarin had an IC₅₀ of 7.5 µM while leucodin managed only 80 µM and achillin 100 µM — roughly a tenfold separation ^{6Reference 6Cheong H et al. · 1998In vitroDesacetylmatricarin, an anti-allergic component from Taraxacum platycarpum — [in vitro]View study →}. In a yarrow antiproliferative screen, desacetylmatricarin was inactive against all three human tumour lines tested ^{20Reference 20Csupor-Löffler B et al. · 2009In vitroAntiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured human tumour cell lines — [in vitro]View study →}. Findings for one are not findings for the other.

Leucodin and achillin are epimers, differing only in the configuration of the C-11 methyl on the lactone ring ^{15,12Reference 15Martinez VM et al. · 1988Conformational analysis of achillin and leukodin — [structural chemistry]View study →Reference 12Tschiggerl C · 2012Guaianolides and volatile compounds in chamomile tea — [phytochemical analysis]View study →}. They co-occur, co-elute closely, and in the yarrow cardiovascular work were tested in parallel and produced similar vasorelaxant and antihypertensive effects ^{1Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →} — so on that one application the epimeric distinction appears not to matter much. That is a specific finding about a specific assay, not a general rule.

Finally, dehydroleucodin (DhL) is a much more studied molecule with a substantial gastroprotective, antitumour and cell-cycle literature. It is leucodin plus an exocyclic methylene ^{16Reference 16Priestap HA et al. · 2011Dehydro-leucodin: a guaiane-type sesquiterpene lactone — [crystal structure]View study →}. Attributing DhL’s results to leucodin is the most consequential error in this cluster — see the next section.

The Missing α-Methylene-γ-Lactone

Almost everything written about sesquiterpene lactones as a class rests on one structural feature: the α-methylene-γ-lactone, an exocyclic C=C conjugated to the lactone carbonyl that acts as a Michael acceptor and alkylates cysteine thiols on proteins. That reactivity is what underlies the class’s NF-κB inhibition, its cytotoxicity, and its notoriety as a contact allergen.

Leucodin does not have it. Leucodin is the 11,13-dihydro compound — a plain C-11 methyl where dehydroleucodin carries the methylidene ^{16,22Reference 16Priestap HA et al. · 2011Dehydro-leucodin: a guaiane-type sesquiterpene lactone — [crystal structure]View study →Reference 22PubChem compound records — Leucodin (CID et al.https://pubchem.ncbi.nlm.nih.gov/compound/167683View study →}. The same is true of achillin, matricin and achillicin; when α-methylene-γ-lactones were finally found in the Achillea millefolium aggregate (in A. setacea), that was reported as a first for the group, explicitly noting that achillin, achillicin, 8-hydroxyachillin, 8-acetoxyachillin and matricin were absent from that species ^{17Reference 17Zitterl-Eglseer K et al. · 1991AnimalSesquiterpene lactones of Achillea setacea with antiphlogistic activity — [mouse in vivo]View study →}.

This has been tested, not just inferred. In the classic study that identified dehydroleucodin as Artemisia douglasiana’s gastroprotective principle, the authors screened related guaianolides to see whether the activity was general to the class. Desacetoxymatricarin — leucodin — showed no cytoprotective activity at all, and the authors concluded that the α-methylene-γ-lactone moiety is in principle a requirement for the antiulcer effect ^{8Reference 8Giordano OS et al. · 1990AnimalThe gastric cytoprotective effect of several sesquiterpene lactones — [rat in vivo]View study →}. A later structure–activity study on guaianolide inhibition of amphibian oocyte meiosis reached a compatible conclusion: inhibition was strongest in lactones carrying two reactive centres, and weakest in those carrying fewer ^{9Reference 9Zapata-Martínez J et al. · 2017In vitroEffect of guaianolides in the meiosis reinitiation of amphibian oocytes — [in vitro]View study →}.

What leucodin does retain is a cyclopentenone — an α,β-unsaturated ketone on the five-membered ring, which is why the group is classed as the 2-oxo-guaianolides ^{10Reference 10Glasl S et al. · 2003TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]View study →}. That is a far weaker electrophile than an α-methylene-γ-lactone, and it is the most plausible structural basis for the modest, high-micromolar activities leucodin does show.

The practical upshot: a claim of the form “sesquiterpene lactones inhibit NF-κB by alkylating cysteine” is uninformative about leucodin, and may be actively wrong. Where leucodin has real activity, the mechanism appears to be something else — ion-channel and receptor-level, not covalent.

What It's Used For

Every result below is in vitro or in rodents. There is no human data of any kind, and no pharmacokinetics.

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. Note that no row here contains any human data; the ceiling for this molecule is low by construction.

01Vasorelaxation & Blood PressurePromising48%Isolate; SHR in vivo + aortic-ring ex vivo with defined mechanism, two papers from one group ^{1,2Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →Reference 2Arias-Durán L et al. · 2020AnimalTracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds — [rat ex vivo]View study →}

02Airway Smooth-Muscle RelaxationShaky34%Isolate identified as the extract’s active principle; mechanism work done on the extract ^{2Reference 2Arias-Durán L et al. · 2020AnimalTracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds — [rat ex vivo]View study →}

03Inflammasome & Hepatic Lipid MetabolismShaky30%Single in-vitro study across three macrophage types + HepG2 ^{3Reference 3Shang Y et al. · 2018In vitroLeucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]View study →}

04COX-2 & PGE2 ModulationShaky26%Single in-vitro study; effect via COX-2 expression, not direct enzyme inhibition ^{4Reference 4Perri F et al. · 2019In vitroNaturally occurring sesquiterpene lactones and their semi-synthetic derivatives modulate PGE2 levels by decreasing COX2 activity and expression — [in vitro]View study →}

05Cholesterol SynthesisShaky20%Single cell-free HMG-CoA reductase assay + docking ^{5Reference 5Khazneh E et al. · 2016In vitroThe chemical composition of Achillea wilhelmsii CView study →}

06Anti-Allergic ActivityShaky14%Weak — IC₅₀ 80 µM, ~10× weaker than the desacetylmatricarin it is confused with ^{6Reference 6Cheong H et al. · 1998In vitroDesacetylmatricarin, an anti-allergic component from Taraxacum platycarpum — [in vitro]View study →}

07Antioxidant ActivityShaky12%Single FRAP figure; the weakest of four isolates from the same plant ^{7Reference 7Anibogwu R et al. · 2024In vitroSesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]View study →}

Mechanisms

The load-bearing row is the last one. Leucodin’s activities are all receptor-, channel- or expression-level; none of them requires — or is explained by — the covalent thiol chemistry that dominates writing about sesquiterpene lactones.

Pharmacokinetics

Nothing is published. No absorption, oral bioavailability, distribution, metabolism, active metabolites, protein binding or half-life data exist for leucodin. The single pharmacokinetically-relevant observation in the whole file is indirect: 50 mg/kg intragastrically lowered blood pressure in rats ^{1Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →}, which establishes that enough of an oral dose survives to act in that species, but says nothing about the fraction absorbed or the plasma concentration reached.

This matters more than usual here. The in-vitro results sit at 80–200 µM ^{3,6Reference 3Shang Y et al. · 2018In vitroLeucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]View study →Reference 6Cheong H et al. · 1998In vitroDesacetylmatricarin, an anti-allergic component from Taraxacum platycarpum — [in vitro]View study →} — concentrations with no demonstrated in-vivo counterpart. Until a plasma-level study exists, none of the cellular findings can be assumed relevant to anyone drinking yarrow tea.

Clinical Trials

There are none. No trial of isolated leucodin has been conducted or registered, in any indication.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for a minor plant constituent, most of leucodin’s file is isolate work — which is a strength of the data even though the data are thin. The cardiovascular result used purified leucodin in aortic rings and in live rats ^{1Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →}; the inflammasome, COX-2, HMG-CoA reductase, mast-cell and FRAP results all used the purified compound ^{3,4,5,6,7Reference 3Shang Y et al. · 2018In vitroLeucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]View study →Reference 4Perri F et al. · 2019In vitroNaturally occurring sesquiterpene lactones and their semi-synthetic derivatives modulate PGE2 levels by decreasing COX2 activity and expression — [in vitro]View study →Reference 5Khazneh E et al. · 2016In vitroThe chemical composition of Achillea wilhelmsii CView study →Reference 6Cheong H et al. · 1998In vitroDesacetylmatricarin, an anti-allergic component from Taraxacum platycarpum — [in vitro]View study →Reference 7Anibogwu R et al. · 2024In vitroSesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]View study →}.

The exception, and it is an important one, is the airway study: there the mechanistic pharmacology (muscarinic antagonism, NO/cGMP, calcium blockade) was characterised on the hexane extract, and leucodin and achillin were isolated afterwards and credited with the activity ^{2Reference 2Arias-Durán L et al. · 2020AnimalTracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds — [rat ex vivo]View study →}. That attribution is reasonable — they were the extract’s major components — but it is an inference, not a direct demonstration.

The transferability caveat runs the other way from the usual one. Leucodin is not what most yarrow preparations deliver: it is a lipophilic constituent recovered from a hexane extract ^{1,2Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →Reference 2Arias-Durán L et al. · 2020AnimalTracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds — [rat ex vivo]View study →}, and 2-oxo-guaianolides of this type are used as chemotype markers precisely because they distinguish non-proazulene-containing Achillea material from the azulene-rich chemotypes ^{10Reference 10Glasl S et al. · 2003TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]View study →}. A water infusion of an azulene-rich sample may contain very little of it. No study has quantified leucodin in any commercial herbal product, and no yarrow trial has been standardised to it.

Prevalence in Nature

Leucodin occurs across the Asteraceae, in three tribes that are not especially close to one another — but it has never been quantified in any of them, so its abundance is described qualitatively everywhere below.

Yarrow (Achillea millefolium) is its best-documented home. In the flower-head hexane extract, leucodin and achillin were reported as the two major components ^{1Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →}. A detailed phytochemical study of a Hungarian A. millefolium taxon isolated leucodin, achillin, desacetylmatricarin and — for the first time — 8α-angeloxy-leucodin and 8α-angeloxy-achillin from flower heads, alongside apigenin, luteolin and centaureidin ^{11Reference 11Glasl S et al. · 2002Sesquiterpenes and flavonoid aglycones from a Hungarian taxon of the Achillea millefolium group — [phytochemical isolation]View study →}. Related Achillea species carry it too: leucodin was one of five compounds isolated from the chloroform fraction of Achillea wilhelmsii ^{5Reference 5Khazneh E et al. · 2016In vitroThe chemical composition of Achillea wilhelmsii CView study →}. Because these 2-oxo-guaianolides are markers for non-proazulene taxa, their presence is chemotype-dependent rather than universal in the A. millefolium aggregate ^{10,17Reference 10Glasl S et al. · 2003TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]View study →Reference 17Zitterl-Eglseer K et al. · 1991AnimalSesquiterpene lactones of Achillea setacea with antiphlogistic activity — [mouse in vivo]View study →}.

In Artemisia, leucodin is reported from the leaves of basin big sagebrush (A. tridentata subsp. tridentata), where it was co-isolated with matricarin and desacetylmatricarin from a chloroform extract ^{7Reference 7Anibogwu R et al. · 2024In vitroSesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]View study →}, and from A. capillaris, the source used for the inflammasome work ^{3Reference 3Shang Y et al. · 2018In vitroLeucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]View study →}. Beyond the Achillea/Artemisia axis it appears in German chamomile — leucodin (explicitly given as ”= desacetoxymatricarin”) was identified in the dichloromethane extract of chamomile tea for the first time in 2012, alongside matricarin, achillin and acetoxyachillin ^{12Reference 12Tschiggerl C · 2012Guaianolides and volatile compounds in chamomile tea — [phytochemical analysis]View study →} — and in the roots of Scorzonera latifolia, a Cichorieae species, where it was one of five compounds from a hexane extract ^{14Reference 14Acıkara ÖB et al. · 2012A new triterpene from Scorzonera latifolia (Fisch. and Mey.) DC. — [phytochemical isolation]View study →}.

Its occurrence in chicory (Cichorium intybus) is documented biochemically rather than by isolation: chicory root enzyme preparations convert (+)-costunolide into leucodin, establishing it as a genuine end-product of that plant’s sesquiterpene-lactone pathway ^{13Reference 13de Kraker JW et al. · 2002Biosynthesis of costunolide, dihydrocostunolide, and leucodin: demonstration of cytochrome P450-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory — [plant enzymology]View study →}. Hydroxylated and glycosylated leucodin derivatives (9α-hydroxyleucodin xylosides) have also been described from Lactuca roots, indicating the skeleton is elaborated further in the lettuce tribe.

No source has been assigned a percentage or mg/g figure.

Discovery & Synthesis

First isolation is not well documented. No original isolation report for leucodin surfaced in a PubMed or Crossref search of the compound and its synonyms; the name predates the indexed literature, and the earliest records found here are structural and pharmacological rather than discovery papers. The molecule’s structure and solution conformation were established by NMR in 1988, in a joint conformational analysis of achillin and “leukodin” that fixed the stereochemical relationship between the two epimers ^{15Reference 15Martinez VM et al. · 1988Conformational analysis of achillin and leukodin — [structural chemistry]View study →}; the absolute configuration of the closely related dehydroleucodin was later confirmed by X-ray crystallography and shown to agree with the leucodin assignment ^{16Reference 16Priestap HA et al. · 2011Dehydro-leucodin: a guaiane-type sesquiterpene lactone — [crystal structure]View study →}. Analytical methods to distinguish leucodin from achillin, desacetylmatricarin and their 8α-angeloxy esters by TLC and HPLC were published in 2003 ^{10Reference 10Glasl S et al. · 2003TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]View study →}.

Biosynthesis is comparatively well characterised for a molecule this obscure. Work on chicory established that the germacranolide (+)-costunolide is the common precursor of the family’s guaianolides, and that an enzyme preparation from chicory roots converts (+)-costunolide into leucodin; the conversion appears to require more than one enzyme, including a cytochrome P450. The preceding step — costunolide synthase, which closes the lactone ring via C6-hydroxylation — was itself shown to be a cytochrome P450 in the same study ^{13Reference 13de Kraker JW et al. · 2002Biosynthesis of costunolide, dihydrocostunolide, and leucodin: demonstration of cytochrome P450-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory — [plant enzymology]View study →}.

Total synthesis: no dedicated total synthesis of leucodin was found. The molecule has instead been used as a natural-product reference scaffold in medicinal chemistry: its vasorelaxant and hypotensive reputation motivated a series of labdane-based synthetic vasodilators built on the structurally similar lactone (+)-sclareolide ^{21Reference 21Carullo G et al. · 2022In vitroNovel labdane diterpenes-based synthetic derivatives: identification of a bifunctional vasodilator that inhibits CaV1.2 and stimulates KCa1.1 channels — [in vitro]View study →}, and it was one of three lactone starting points in a semi-synthetic anti-inflammatory series ^{4Reference 4Perri F et al. · 2019In vitroNaturally occurring sesquiterpene lactones and their semi-synthetic derivatives modulate PGE2 levels by decreasing COX2 activity and expression — [in vitro]View study →}. All material used in research to date has been obtained by extraction and chromatographic isolation from plant sources, not by synthesis.

Patents: not yet researched.

Toxicity & Safety

Leucodin carries a low flag — but that reflects the absence of any toxicity signal in a very small dataset, not the presence of a safety package. No repeat-dose, genotoxicity, reproductive or organ-toxicity study of isolated leucodin exists, and no LD₅₀ has been reported.

Safety at a Glance

✅ Low / no toxicityDaisy-family allergy

• No cytotoxicity signal in the two screens that looked. Non-toxic up to 200 µM across mouse peritoneal, bone-marrow-derived and human THP-1 macrophages ^{3Reference 3Shang Y et al. · 2018In vitroLeucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]View study →}; NCI-60 one-dose results unremarkable ^{7Reference 7Anibogwu R et al. · 2024In vitroSesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]View study →}.
• Lacks the reactive α-methylene-γ-lactone that drives sesquiterpene-lactone thiol alkylation, cytotoxicity and sensitisation ^{8,17Reference 8Giordano OS et al. · 1990AnimalThe gastric cytoprotective effect of several sesquiterpene lactones — [rat in vivo]View study →Reference 17Zitterl-Eglseer K et al. · 1991AnimalSesquiterpene lactones of Achillea setacea with antiphlogistic activity — [mouse in vivo]View study →} — the class’s headline hazard is structurally absent here.
• Asteraceae contact allergy. The plants that carry leucodin — yarrow, chamomile, sagebrush — are established causes of allergic contact dermatitis and are represented in the sesquiterpene-lactone and Compositae patch-test mixes ^{18,19Reference 18Calapai G et al. · 2014ReviewContact dermatitis as an adverse reaction to some topically used European herbal medicinal products — part 1: Achillea millefolium–Curcuma longa — [review]View study →Reference 19Jovanović M et al. · 2004Clinical trialContact allergy to Compositae plants in patients with atopic dermatitis — [patch-test study in patients]View study →}. Leucodin itself has not been tested as an allergen.
• Theoretical additive hypotension. The one reproduced pharmacology is blood-pressure lowering via calcium-channel blockade and NO release ^{1Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →}; additive effects with antihypertensive drugs are plausible in principle but have never been studied.
• No toxicology package at all. No repeat-dose, genotoxicity or reproductive data; no human exposure data; no pharmacokinetics. Absence of findings here is absence of study, not evidence of safety.

Full Safety & Interactions Detail

What has actually been measured. Leucodin showed no significant toxicity in macrophages at concentrations up to 200 µM over the exposure used in the inflammasome study ^{3Reference 3Shang Y et al. · 2018In vitroLeucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]View study →}, and its one-dose NCI-60 screen across 60 human tumour lines was described as unremarkable — in contrast to the co-isolated flavonoid from the same plant, which was potent enough to warrant five-dose follow-up ^{7Reference 7Anibogwu R et al. · 2024In vitroSesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]View study →}. Both are screening observations rather than toxicology, but they are consistent with a molecule that lacks the class’s alkylating warhead.

The structural argument, and its limit. Sesquiterpene-lactone toxicity and allergenicity are largely attributed to the α-methylene-γ-lactone Michael acceptor, which leucodin does not have ^{8,16,17Reference 8Giordano OS et al. · 1990AnimalThe gastric cytoprotective effect of several sesquiterpene lactones — [rat in vivo]View study →Reference 16Priestap HA et al. · 2011Dehydro-leucodin: a guaiane-type sesquiterpene lactone — [crystal structure]View study →Reference 17Zitterl-Eglseer K et al. · 1991AnimalSesquiterpene lactones of Achillea setacea with antiphlogistic activity — [mouse in vivo]View study →}. That is a genuine risk reducer relative to helenalin- or parthenolide-type lactones. It is not a clean bill: leucodin retains an α,β-unsaturated cyclopentenone, a weaker electrophile, and structure–activity work on guaianolides treats that cyclopentanone system as a real if secondary reactive centre ^{9Reference 9Zapata-Martínez J et al. · 2017In vitroEffect of guaianolides in the meiosis reinitiation of amphibian oocytes — [in vitro]View study →}.

Asteraceae contact dermatitis. This is a plant-level and class-level caution that a leucodin page has to carry, because the herbs that deliver leucodin are the ones implicated. Achillea millefolium is among the topically used European herbal medicinal products reviewed specifically for contact dermatitis as an adverse reaction ^{18Reference 18Calapai G et al. · 2014ReviewContact dermatitis as an adverse reaction to some topically used European herbal medicinal products — part 1: Achillea millefolium–Curcuma longa — [review]View study →}, and Compositae sensitivity is routinely detected by patch testing with a sesquiterpene lactone mix plus a Compositae mix containing yarrow, chamomile, arnica, tansy and feverfew extracts — in one series of atopic-dermatitis patients, 30% were Compositae-sensitive with a 10% sesquiterpene-lactone-mix detection rate ^{19Reference 19Jovanović M et al. · 2004Clinical trialContact allergy to Compositae plants in patients with atopic dermatitis — [patch-test study in patients]View study →}. Which individual lactones drive that response in yarrow has not been resolved, and leucodin has not been tested as a single patch-test allergen.

Interactions. No enzyme- or transporter-level interaction data exist — no CYP inhibition/induction screen, no P-gp work, no protein-binding measurement. The only mechanism-based interaction worth flagging is pharmacodynamic: additive blood-pressure lowering with antihypertensives, calcium-channel blockers or nitrates, inferred from the mechanism ^{1Reference 1Arias-Durán L et al. · 2021AnimalAntihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]View study →} and never tested.

Reproductive note (prose only). No reproductive or developmental study of isolated leucodin exists. One structure–activity study found that guaianolides can inhibit meiotic resumption in amphibian oocytes, with the effect weakest in lactones carrying fewer reactive centres — leucodin’s category ^{9Reference 9Zapata-Martínez J et al. · 2017In vitroEffect of guaianolides in the meiosis reinitiation of amphibian oocytes — [in vitro]View study →}; this is a comparative-biology assay in Rhinella arenarum, not a mammalian reproductive-toxicity finding, and should not be read as one. Pregnancy and lactation decisions belong to the herb or product page where intake is decided, not to a molecule page.

Dosage

There is no human dose for leucodin, and nothing is standardised to it. The figures below are the doses and concentrations used in research.

Human exposure is entirely indirect — through yarrow, chamomile tea, sagebrush and chicory, none of which are marketed with a leucodin content figure, and at least one of which (yarrow) contains it only in certain chemotypes ^{10,12Reference 10Glasl S et al. · 2003TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]View study →Reference 12Tschiggerl C · 2012Guaianolides and volatile compounds in chamomile tea — [phytochemical analysis]View study →}. Because no pharmacokinetic study exists, there is no way to convert the rat dose into a herbal equivalent. These are doses studied in research and are not a personal recommendation.

References

1. Arias-Durán L, et al. (2021). Antihypertensive and vasorelaxant effect of leucodin and achillin isolated from Achillea millefolium through calcium channel blockade and NO production: in vivo, functional ex vivo and in silico studies — [rat in vivo]. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/33610712/
2. Arias-Durán L, et al. (2020). Tracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds — [rat ex vivo]. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/32035218/
3. Shang Y, et al. (2018). Leucodin attenuates inflammatory response in macrophages and lipid accumulation in steatotic hepatocytes via P2x7 receptor pathway: a potential role in alcoholic liver disease — [in vitro]. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/30099341/
4. Perri F, et al. (2019). Naturally occurring sesquiterpene lactones and their semi-synthetic derivatives modulate PGE2 levels by decreasing COX2 activity and expression — [in vitro]. Heliyon. https://pubmed.ncbi.nlm.nih.gov/30976671/
5. Khazneh E, et al. (2016). The chemical composition of Achillea wilhelmsii C. Koch and its desirable effects on hyperglycemia, inflammatory mediators and hypercholesterolemia as risk factors for cardiometabolic disease — [in vitro]. Molecules. https://pubmed.ncbi.nlm.nih.gov/27023504/
6. Cheong H, et al. (1998). Desacetylmatricarin, an anti-allergic component from Taraxacum platycarpum — [in vitro]. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/9741305/
7. Anibogwu R, et al. (2024). Sesquiterpene lactones and flavonoid from the leaves of basin big sagebrush (Artemisia tridentata subsp. tridentata): isolation, characterization and biological activities — [in vitro]. Molecules. https://pubmed.ncbi.nlm.nih.gov/38398555/
8. Giordano OS, et al. (1990). The gastric cytoprotective effect of several sesquiterpene lactones — [rat in vivo]. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/2095374/
9. Zapata-Martínez J, et al. (2017). Effect of guaianolides in the meiosis reinitiation of amphibian oocytes — [in vitro]. Zygote. https://pubmed.ncbi.nlm.nih.gov/27806737/
10. Glasl S, et al. (2003). TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives — [analytical chemistry]. Pharmazie. https://pubmed.ncbi.nlm.nih.gov/12889533/
11. Glasl S, et al. (2002). Sesquiterpenes and flavonoid aglycones from a Hungarian taxon of the Achillea millefolium group — [phytochemical isolation]. Zeitschrift für Naturforschung C. https://pubmed.ncbi.nlm.nih.gov/12562079/
12. Tschiggerl C, Bucar F (2012). Guaianolides and volatile compounds in chamomile tea — [phytochemical analysis]. Plant Foods for Human Nutrition. https://pubmed.ncbi.nlm.nih.gov/22410959/
13. de Kraker JW, et al. (2002). Biosynthesis of costunolide, dihydrocostunolide, and leucodin: demonstration of cytochrome P450-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory — [plant enzymology]. Plant Physiology. https://pubmed.ncbi.nlm.nih.gov/12011356/
14. Acıkara ÖB, et al. (2012). A new triterpene from Scorzonera latifolia (Fisch. and Mey.) DC. — [phytochemical isolation]. Natural Product Research. https://pubmed.ncbi.nlm.nih.gov/21995805/
15. Martinez VM, Muñoz-Zamora A, Joseph-Nathan P (1988). Conformational analysis of achillin and leukodin — [structural chemistry]. Journal of Natural Products. https://doi.org/10.1021/np50056a005
16. Priestap HA, et al. (2011). Dehydro-leucodin: a guaiane-type sesquiterpene lactone — [crystal structure]. Acta Crystallographica Section E. https://pubmed.ncbi.nlm.nih.gov/22199945/
17. Zitterl-Eglseer K, et al. (1991). Sesquiterpene lactones of Achillea setacea with antiphlogistic activity — [mouse in vivo]. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/1798798/
18. Calapai G, et al. (2014). Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products — part 1: Achillea millefolium–Curcuma longa — [review]. Contact Dermatitis. https://pubmed.ncbi.nlm.nih.gov/24621152/
19. Jovanović M, et al. (2004). Contact allergy to Compositae plants in patients with atopic dermatitis — [patch-test study in patients]. Medicinski Pregled. https://pubmed.ncbi.nlm.nih.gov/15503788/
20. Csupor-Löffler B, et al. (2009). Antiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured human tumour cell lines — [in vitro]. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/19107850/
21. Carullo G, et al. (2022). Novel labdane diterpenes-based synthetic derivatives: identification of a bifunctional vasodilator that inhibits CaV1.2 and stimulates KCa1.1 channels — [in vitro]. Marine Drugs. https://pubmed.ncbi.nlm.nih.gov/36005518/
22. PubChem compound records — Leucodin (CID 167683), Desacetylmatricarin (CID 6713966), Achillin (CID 442139), Matricarin (CID 3083923), Dehydroleucodin (CID 73440) — [chemical database]. https://pubchem.ncbi.nlm.nih.gov/compound/167683

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