Psilostachyin

Psilostachyin at a Glance

Psilostachyin is a sesquiterpene dilactone of the pseudoguaianolide (ambrosanolide) type — two lactone rings on a fifteen-carbon skeleton, one of them a reactive α-methylene-γ-lactone. It was isolated from the western ragweed Ambrosia psilostachya and named for it in 1966 ^{1Reference 1Mabry TJ et al. · 1966The structure of psilostachyin, a new sesquiterpene dilactone from Ambrosia psilostachyaView study →}.

Almost everything published about the isolated molecule is antiparasitic, and almost all of it comes from Argentine pharmacognosy groups working on Ambrosia species native to the Río de la Plata basin. Psilostachyin kills Trypanosoma cruzi (the agent of Chagas disease) and Leishmania promastigotes at sub-microgram-per-millilitre concentrations in vitro ^{2Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →}, inhibits Plasmodium falciparum including a chloroquine-resistant strain ^{4Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}, and interacts with hemin rather than with the sterol pathway its close relative psilostachyin C attacks ^{7Reference 7Sülsen VP et al. · 2016In vitroMode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on Trypanosoma cruzi — in vitroView study →}. It is also, in agricultural work, the most potent molluscicide in ragweed ^{12Reference 12Ding W et al. · 2018Ambrosia artemisiifolia as a potential resource for management of golden apple snails, Pomacea canaliculata (Lamarck)View study →}.

Two honest limits frame the whole page. First, the selectivity indices are modest — 3.8 to 11.6 against P. falciparum, around 5 against a normal fibroblast line — which is what you expect from a thiol-alkylating electrophile, and which is why none of this has gone anywhere clinically ^{4,10Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}. Second, the one in-vivo antitrypanosomal success ^{2Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →} failed to replicate in an independent laboratory using a different mouse model, where psilostachyin produced 100% mortality ^{6Reference 6da Silva CF et al. · 2013In vitroActivities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected miceView study →}. There are no human data, no pharmacokinetics, and no clinical trials.

Is Psilostachyin Really a Mugwort Compound?

This page was commissioned as a mugwort constituent. It is not one, on the evidence available, and the honest version of that answer is more useful than the page it was meant to be.

What the molecule’s own literature says. Psilostachyin is an Ambrosia compound. It is named for Ambrosia psilostachya ^{1Reference 1Mabry TJ et al. · 1966The structure of psilostachyin, a new sesquiterpene dilactone from Ambrosia psilostachyaView study →}, and every isolation reported in the indexed literature comes from that genus — A. artemisiifolia ^{9,13Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →Reference 13Wang PH et al. · 1993Wang PH, Xu J, Wu MY (1993). [Chemical constituents of ragweed (Ambrosia artemisiifolia L.)]. Zhongguo Zhong Yao Za Zhi. https://pubmed.ncbi.nlm.nih.gov/8352903/View study →}, A. tenuifolia ^{2,4Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}, A. scabra ^{5,7Reference 5Sülsen VP et al. · 2013In vitroNatural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatidsView study →Reference 7Sülsen VP et al. · 2016In vitroMode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on Trypanosoma cruzi — in vitroView study →} and A. arborescens ^{14,15Reference 14Guillen E et al. · 2024Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activityView study →Reference 15De Leo M et al. · 2010Sesquiterpenes and diterpenes from Ambrosia arborescensView study →}. A PubMed search for psilostachyin returns 24 records in total; a search for psilostachyin AND Artemisia returns one, and that one record is about psilostachyin C, a different molecule (checked 31 July 2026).

Where the mugwort claim comes from. It traces to a widely-cited 2020 review of Artemisia vulgaris, which states that a characteristic feature of the species is the presence of “psilostachyin, psilostachyin C, and vulgarin,” lists the content of both psilostachyins as not available, and cites two sources for the claim ^{18Reference 18Ekiert H et al. · 2020ReviewSignificance of Artemisia vulgaris L. (common mugwort) in the history of medicine and its possible contemporary applications substantiated by phytochemical and pharmacological studies — reviewView study →}. Those two sources are a practitioner handbook of herbal drugs, and a 1991 Phytochemistry paper titled “Two eudesmane acids from Artemisia vulgaris” — a paper about a structurally unrelated class of compound ^{24Reference 24Marco JA et al. · 1991Two eudesmane acids from Artemisia vulgarisView study →}. Neither is a primary report of psilostachyin from mugwort.

What modern work on the plant found instead. The most thorough recent sesquiterpene-lactone study of A. vulgaris isolated twenty-two lactones from the aerial parts — twelve of them new — and every one was a guaianolide. Psilostachyin was not among them ^{17Reference 17Chen XY et al. · 2022In vitroSesquiterpene lactones from Artemisia vulgaris L. as potential NO inhibitors in LPS-induced RAW264.7 macrophage cells — in vitroView study →}.

The chemotaxonomy points the same way. Pseudoguaianolides of the ambrosanolide type are the signature of the subtribe Ambrosiinae — Ambrosia, Xanthium, Parthenium. Artemisia sits in a different subtribe and characteristically produces eudesmanolides (such as vulgarin), guaianolides and germacranolides. A ragweed pseudoguaianolide in mugwort would be chemically surprising, not expected.

The verdict, stated plainly. The occurrence of psilostachyin in mugwort is unconfirmed. It may yet be present as a trace or chemotype-specific constituent — absence of evidence in a chemotype-variable species is not proof — but no primary isolation supports it, and nothing here should be read as pharmacology for mugwort. The related worklist note describing psilostachyin as mugwort’s “digestive-bitter marker” is likewise unsupported: no study has measured the taste, bitter-receptor activity or digestive effect of this molecule (psilostachyin AND bitter → 0 PubMed records, psilostachyin AND taste → 0).

The α-Methylene-γ-Lactone — Present, and It Explains the Selectivity Ceiling

Unlike its mugwort-associated neighbour vulgarin, psilostachyin does carry the class warhead, and this is the single most useful fact for reading its data.

Its formula is C₁₅H₂₀O₅ (MW 280.32), and its structure is a spiro-fused dilactone: a γ-butyrolactone spiro-linked at C-7 to a seven-membered carbocycle bearing a second γ-lactone whose α-carbon carries an exocyclic methylene conjugated to the lactone carbonyl. That exocyclic C=CH₂ is a Michael acceptor — it adds cysteine thiols on essentially any protein it meets.

The experimental confirmation is direct rather than assumed. When Sturgeon and colleagues eliminated the α,β-unsaturated carbonyl from psilostachyins A and C, the cell-cycle-checkpoint activity disappeared, which the authors read as evidence that the compounds bind covalently to their targets by Michael addition ^{9Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →}. The parasite work agrees from a different angle: psilostachyin’s antiproliferative effect on T. cruzi was partially blocked by added glutathione, and fully blocked in Leishmania mexicana at 1.5 mM glutathione — a thiol competing the electrophile away ^{3,8Reference 3Sülsen V et al. · 2010In vitroAntiproliferative effect and ultrastructural alterations induced by psilostachyin on Trypanosoma cruzi — in vitroView study →Reference 8Barrera P et al. · 2013In vitroNatural sesquiterpene lactones induce oxidative stress in Leishmania mexicana — in vitroView study →}.

Three consequences follow, and they should be applied to every number below:

• “Inhibits NF-κB in vitro” would say almost nothing about this molecule specifically. Thiol alkylation is a class property shared by parthenolide, costunolide, helenalin and hundreds of others. (In psilostachyin’s case the question is moot — a PubMed search for psilostachyin AND NF-kB returns zero records.)
• Selectivity is structurally capped. A reagent that alkylates thiols indiscriminately will hit host cells alongside parasites, and psilostachyin’s measured selectivity indices — 11.6 against chloroquine-sensitive P. falciparum, 3.8 against the resistant W2 strain, roughly 5 against normal human lung fibroblasts — are exactly the modest numbers that predicts ^{4,10Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}. A trypanocidal IC50 quoted without a selectivity index is close to meaningless here.
• It is a plausible contact allergen. The sesquiterpene-lactone patch-test mix is built from three α-methylene lactones precisely because that group is the sensitising motif ^{19Reference 19Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspectsView study →}. Psilostachyin has never been patch-tested, but structurally it belongs to the sensitising set.

The one place selectivity is genuinely good is against Leishmania: an IC50 of 0.12 µg/mL on promastigotes with “high selectivity,” a two-order-of-magnitude gap that the Plasmodium work never reproduced ^{2Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →}.

Not Artemisinin

Because psilostachyin’s headline data are antiparasitic and it has been mis-filed under Artemisia, it invites a specific and serious confusion.

Artemisinin is a different molecule with a different mechanism. Artemisinin is a sesquiterpene lactone endoperoxide from Artemisia annua (sweet wormwood); its antimalarial action depends entirely on iron-mediated cleavage of that endoperoxide bridge, and it is a frontline human antimalarial drug. Psilostachyin has no endoperoxide. Its in-vitro antiplasmodial IC50 of 2.1 µM against the F32 strain sits about seventy-fold weaker than chloroquine tested in the same run (0.03 µM), with a selectivity index of 11.6 ^{4Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}.

Nothing about artemisinin’s clinical antimalarial record transfers to psilostachyin. They are not the same molecule, not from the same genus, and not the same class of mechanism.

Ragweed Pollen Allergy vs. Sesquiterpene-Lactone Dermatitis

Ragweed is best known to most readers as an allergy plant, so it is worth separating two things that are routinely conflated. They are different molecules, different immune mechanisms, different tissues and different clinical pictures.

	Ragweed pollen allergy	Sesquiterpene-lactone contact dermatitis
Trigger	Pollen proteins — chiefly the major allergen Amb a 1, plus cross-reactive profilin and calcium-binding allergens 20Reference 20Zbîrcea LE et al. · 2023Clinical trialRelationship between IgE levels specific for ragweed pollen extract, Amb a 1 and cross-reactive allergen molecules — in patientsView study →	Small-molecule lactones in leaf/stem resin, acting as haptens 19Reference 19Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspectsView study →
Immunology	IgE-mediated, immediate (type I) hypersensitivity	T-cell-mediated, delayed (type IV) hypersensitivity
Route	Inhaled pollen	Skin contact with plant sap or dust
Picture	Seasonal rhinitis, conjunctivitis, asthma	Eczematous, often airborne-pattern dermatitis
Test	Specific IgE / skin-prick to pollen extract or Amb a 1 20Reference 20Zbîrcea LE et al. · 2023Clinical trialRelationship between IgE levels specific for ragweed pollen extract, Amb a 1 and cross-reactive allergen molecules — in patientsView study →	Patch test to the sesquiterpene-lactone mix 19Reference 19Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspectsView study →
Where psilostachyin sits	Nowhere — it is not a pollen protein	Structurally in the sensitising class; never itself tested

The practical point: someone with hay fever from ragweed pollen is reacting to Amb a 1 and its relatives, not to psilostachyin, and a psilostachyin exposure is not a pollen-allergy exposure. Conversely, Compositae contact dermatitis is a hapten phenomenon that has nothing to do with IgE or pollen season. The mean prevalence of positive patch-test reactions to the sesquiterpene-lactone mix is around 1% in Europe and 0.8% in North America ^{19Reference 19Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspectsView study →} — a genuinely different population from ragweed hay-fever sufferers.

What It's Used For

The isolate literature is small, coherent and almost entirely preclinical: roughly a dozen primary studies, dominated by antiprotozoal work from Buenos Aires, with a secondary cytotoxicity strand and one agricultural molluscicide paper. There is no human study of psilostachyin.

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. Every score is capped low because no human data exist, and the antitrypanosomal score is capped further by a failed independent in-vivo replication.

01Antitrypanosomal ActivityShaky42%Four in-vitro studies plus two conflicting mouse studies ^{2,3,5,6,7Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 3Sülsen V et al. · 2010In vitroAntiproliferative effect and ultrastructural alterations induced by psilostachyin on Trypanosoma cruzi — in vitroView study →Reference 5Sülsen VP et al. · 2013In vitroNatural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatidsView study →Reference 6da Silva CF et al. · 2013In vitroActivities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected miceView study →Reference 7Sülsen VP et al. · 2016In vitroMode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on Trypanosoma cruzi — in vitroView study →}

02Leishmanicidal ActivityShaky32%Two in-vitro studies; best selectivity of any target ^{2,8Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 8Barrera P et al. · 2013In vitroNatural sesquiterpene lactones induce oxidative stress in Leishmania mexicana — in vitroView study →}

03Antiplasmodial ActivityShaky28%One in-vitro study, two strains, selectivity index reported ^{4Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}

04Cytotoxicity and the G2 CheckpointShaky26%Three in-vitro studies across human and murine lines ^{9,10,11Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →Reference 11Martino R et al. · 2015In vitroSesquiterpene lactones from Ambrosia spp. are active against a murine lymphoma cell line by inducing apoptosis and cell cycle arrest — in vitroView study →}

05Molluscicidal ActivityShaky22%Field and laboratory agricultural work; not a human application ^{12,13Reference 12Ding W et al. · 2018Ambrosia artemisiifolia as a potential resource for management of golden apple snails, Pomacea canaliculata (Lamarck)View study →Reference 13Wang PH et al. · 1993Wang PH, Xu J, Wu MY (1993). [Chemical constituents of ragweed (Ambrosia artemisiifolia L.)]. Zhongguo Zhong Yao Za Zhi. https://pubmed.ncbi.nlm.nih.gov/8352903/View study →}

06Anti-Inflammatory PotentialShaky8%One semisynthesis paper; no numeric outcome published in the abstract ^{16Reference 16Chib R et al. · 2011In vitroPsilostachyin, acetylated pseudoguaianolides and their analogues: preparation and evaluation of their anti-inflammatory potential — in vitroView study →}

Mechanisms

The load-bearing point is the top row. Psilostachyin is a reactive electrophile first and a targeted agent second, which is why its potency numbers look good and its selectivity numbers do not.

Pharmacokinetics

Nothing is known. A PubMed search for psilostachyin AND pharmacokinetics returns zero records (checked 31 July 2026). No absorption, distribution, plasma concentration, oral bioavailability, metabolism, active metabolite, half-life or excretion data have been published for this molecule.

What can be said is indirect and cautionary. The in-vivo dosing that exists is parenteral or unstated and spans 0.5–50 mg/kg/day in mice ^{6Reference 6da Silva CF et al. · 2013In vitroActivities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected miceView study →}, and the two mouse studies disagree completely on outcome ^{2,6Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 6da Silva CF et al. · 2013In vitroActivities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected miceView study →} — a discrepancy that pharmacokinetics would be the natural way to explain and which nobody has attempted. More fundamentally, an α-methylene-γ-lactone is a glutathione substrate: the glutathione-reversibility demonstrated in both parasite systems ^{3,8Reference 3Sülsen V et al. · 2010In vitroAntiproliferative effect and ultrastructural alterations induced by psilostachyin on Trypanosoma cruzi — in vitroView study →Reference 8Barrera P et al. · 2013In vitroNatural sesquiterpene lactones induce oxidative stress in Leishmania mexicana — in vitroView study →} is exactly what would be expected to happen to it in mammalian plasma and liver, where glutathione is abundant. That predicts rapid conjugation and poor systemic delivery of the intact electrophile, and it is a strong reason not to read any in-vitro IC50 here as an achievable exposure.

That is an inference from chemistry, not a measured finding. A single rodent pharmacokinetic study would change the ceiling of it more than any other experiment.

Clinical Trials

There are no clinical trials of psilostachyin — completed, ongoing, planned or terminated. The molecule has never been administered to a human in a reported study.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule has the opposite profile to most plant constituents: the isolate is nearly all there is, and the whole-plant literature is the thin part.

Every pharmacological finding above used purified psilostachyin, isolated by the studying group from a named Ambrosia species — A. tenuifolia for the trypanocidal, leishmanicidal and antiplasmodial work ^{2,4Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}, A. scabra for the amastigote and mode-of-action studies ^{5,7Reference 5Sülsen VP et al. · 2013In vitroNatural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatidsView study →Reference 7Sülsen VP et al. · 2016In vitroMode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on Trypanosoma cruzi — in vitroView study →}, A. artemisiifolia for the checkpoint and colon-cancer work ^{9,10Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}, and A. arborescens for the green-extraction chemistry ^{14Reference 14Guillen E et al. · 2024Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activityView study →}. That is normally a strength — the numbers belong to the molecule, not to an undefined extract.

The whole-plant comparisons that exist are small and mostly favour the extract’s complexity rather than the isolate. The A. tenuifolia organic extract was itself antiplasmodial at IC50 2 µg/mL, in the same range as its purified lactones ^{4Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}. In the A. elatior/A. scabra screen, cumanin outperformed psilostachyin in vivo, producing an eight-fold parasitaemia reduction and 66% survival where benznidazole and psilostachyin did less ^{5Reference 5Sülsen VP et al. · 2013In vitroNatural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatidsView study →}. In the murine lymphoma panel, psilostachyin C outperformed psilostachyin on both activity and toxicity ^{11Reference 11Martino R et al. · 2015In vitroSesquiterpene lactones from Ambrosia spp. are active against a murine lymphoma cell line by inducing apoptosis and cell cycle arrest — in vitroView study →}.

The transferability caveat runs one specific way here: do not read any of this onto a herb here. No monograph plant here is a confirmed source of psilostachyin. Ragweed is not a medicinal herb, and the mugwort attribution does not hold up (see above). The molecule’s pharmacology is currently orphaned from any herbal use.

Prevalence in Nature

Psilostachyin is, on the published record, an Ambrosia compound — a genus of North and South American ragweeds in the Asteraceae, subtribe Ambrosiinae. Confirmed occurrences, each tied to a named plant by isolation rather than by database annotation:

Species	Note	Evidence
Ambrosia psilostachya	Western ragweed — the naming species	Structure report, 1966 1Reference 1Mabry TJ et al. · 1966The structure of psilostachyin, a new sesquiterpene dilactone from Ambrosia psilostachyaView study →
Ambrosia artemisiifolia	Common ragweed	Repeated isolation from aerial parts 9,10,12,13Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →Reference 12Ding W et al. · 2018Ambrosia artemisiifolia as a potential resource for management of golden apple snails, Pomacea canaliculata (Lamarck)View study →Reference 13Wang PH et al. · 1993Wang PH, Xu J, Wu MY (1993). [Chemical constituents of ragweed (Ambrosia artemisiifolia L.)]. Zhongguo Zhong Yao Za Zhi. https://pubmed.ncbi.nlm.nih.gov/8352903/View study →
Ambrosia tenuifolia	Argentine ragweed	Bioassay-guided isolation 2,4Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →
Ambrosia scabra	South American ragweed	Isolated alongside cordilin 5,7Reference 5Sülsen VP et al. · 2013In vitroNatural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatidsView study →Reference 7Sülsen VP et al. · 2016In vitroMode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on Trypanosoma cruzi — in vitroView study →
Ambrosia arborescens	Andean shrub ragweed	Main isolated compound; related derivatives detected by LC-MS 14,15Reference 14Guillen E et al. · 2024Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activityView study →Reference 15De Leo M et al. · 2010Sesquiterpenes and diterpenes from Ambrosia arborescensView study →

Quantities are essentially unpublished. No percent-dry-weight figure for psilostachyin in any plant was located. The nearest thing to a number is preparative: a 2024 green-chemistry study isolated psilostachyin from A. arborescens crude extracts in 0.40% yield from a methanol maceration and 0.44% from a microwave-assisted ethyl-lactate extraction, describing it as the main compound of the plant ^{14Reference 14Guillen E et al. · 2024Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activityView study →}. That is an isolation yield from extract, not a tissue content, and should not be quoted as an abundance.

Related molecules travel with it, and the names are easy to mix up. A. artemisiifolia yields psilostachyin, psilostachyin B (a distinct dilactone, first characterised in 1977) and psilostachyin C together ^{13Reference 13Wang PH et al. · 1993Wang PH, Xu J, Wu MY (1993). [Chemical constituents of ragweed (Ambrosia artemisiifolia L.)]. Zhongguo Zhong Yao Za Zhi. https://pubmed.ncbi.nlm.nih.gov/8352903/View study →}; A. arborescens additionally shows dehydropsilostachyin and 10α-hydroxy-11,13-dihydro-5-epi-psilostachyin ^{14,15Reference 14Guillen E et al. · 2024Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activityView study →Reference 15De Leo M et al. · 2010Sesquiterpenes and diterpenes from Ambrosia arborescensView study →}; and A. artemisiifolia also gives the seco-psilostachyinolides 1′-noraltamisin and 1,10-dihydro-1′-noraltamisin ^{10Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}. Keep the numbers attached to the right member — psilostachyin B was inactive in the checkpoint assay where psilostachyin A and C were active ^{9Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →}.

Outside Ambrosia, the record is for the relatives, not for psilostachyin itself. Psilostachyin C — not psilostachyin — has been isolated from Achillea millefolium (yarrow), in what was the first report of seco-pseudoguaianolides in that genus ^{21Reference 21Csupor-Löffler B et al. · 2009In vitroAntiproliferative effect of flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured human tumour cell lines — in vitroView study →}. A PubMed search for psilostachyin AND Xanthium or AND Parthenium returns zero records for either genus, despite both sitting in the same subtribe.

Discovery & Synthesis

First isolation. Psilostachyin was isolated from Ambrosia psilostachya DC. and named for it; T. J. Mabry, H. E. Miller, H. B. Kagan and W. Renold reported the structure of “a new sesquiterpene dilactone” in Tetrahedron in 1966 ^{1Reference 1Mabry TJ et al. · 1966The structure of psilostachyin, a new sesquiterpene dilactone from Ambrosia psilostachyaView study →}. The same Texas group characterised the rest of the family in the same period — psilostachyin C in the Journal of Organic Chemistry in 1966 and psilostachyin B in Tetrahedron in 1966 — making A. psilostachya the type source for the whole series. Psilostachyin B was later independently isolated and identified from common ragweed by Raszeja and Gill in 1977.

Synthesis. There is no reported total synthesis of psilostachyin itself. A PubMed search for psilostachyin AND total synthesis returns exactly one record, and it is for the sibling molecule: Li and colleagues published a total synthesis of psilostachyin C in the Journal of Organic Chemistry in 2011, framed around its role as a G2/M DNA-damage-checkpoint inhibitor ^{23Reference 23Li C et al. · 2011Total synthesis of the G2/M DNA damage checkpoint inhibitor psilostachyin CView study →}. What exists for psilostachyin is semisynthesis: a 2011 study prepared psilostachyin along with acetylated pseudoguaianolides and analogues, confirming the semi-synthetic product’s structure by X-ray crystallography ^{16Reference 16Chib R et al. · 2011In vitroPsilostachyin, acetylated pseudoguaianolides and their analogues: preparation and evaluation of their anti-inflammatory potential — in vitroView study →}.

Manufacture today. None at scale. Psilostachyin is a research chemical obtained by extraction and chromatography from Ambrosia aerial parts by the groups that study it. The most recent methodological work is about making that extraction greener rather than larger — replacing methanol maceration with microwave-assisted extraction into ethyl lactate, at comparable yield ^{14Reference 14Guillen E et al. · 2024Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activityView study →}.

Patents: not yet researched.

Toxicity & Safety

Psilostachyin carries a moderate flag. Not because a toxicology package showed harm — no toxicology package exists — but because of what the molecule is and what the activity data imply: a reactive Michael acceptor that kills protozoa, mammalian cells and molluscs at overlapping concentrations, with selectivity indices in the single digits to low tens.

Safety at a Glance

⚠️ Moderate toxicityDaisy-family allergy

• Low selectivity is the defining safety fact. Selectivity indices of 3.8–11.6 against P. falciparum and ~5 against normal human fibroblasts mean the concentrations that kill parasites and tumour cells are close to the ones that harm normal cells ^{4,10Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}.
• A thiol-alkylating electrophile. The α-methylene-γ-lactone adds covalently to cysteine residues on essentially any protein; its effects are partly reversed by glutathione, which is the signature of non-specific reactivity rather than a defined target ^{3,8,9Reference 3Sülsen V et al. · 2010In vitroAntiproliferative effect and ultrastructural alterations induced by psilostachyin on Trypanosoma cruzi — in vitroView study →Reference 8Barrera P et al. · 2013In vitroNatural sesquiterpene lactones induce oxidative stress in Leishmania mexicana — in vitroView study →Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →}.
• Compositae/sesquiterpene-lactone contact-allergy class. Never patch-tested itself, but structurally it belongs to the group that defines the sesquiterpene-lactone patch-test mix ^{19Reference 19Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspectsView study →}. This is separate from ragweed pollen allergy.
• No toxicology and no pharmacokinetics of any kind. No LD50, no repeat-dose study, no genotoxicity, no carcinogenicity, no reproductive study, no CYP or transporter data, no plasma measurement. Silence, not clearance.
• No human exposure route is established. There is no supplement, no medicine and no confirmed herbal source here, so the practical exposure question does not currently arise.

Full Safety & Interactions Detail

What has actually been observed. The in-vivo safety observations are incidental to efficacy work. In the 2008 mouse study, psilostachyin-treated animals survived at 100% with lower parasitaemia ^{2Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →}. In the 2013 independent study, psilostachyin A at 0.5–50 mg/kg/day reached 100% animal mortality in the acute T. cruzi model — but in an infection model, so mortality cannot be cleanly attributed to compound toxicity rather than to treatment failure ^{6Reference 6da Silva CF et al. · 2013In vitroActivities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected miceView study →}. The paper explicitly notes psilostachyin A “was not effective” at those doses. That ambiguity is itself the finding: the only mammalian dose range published for this molecule comes with an unresolved mortality signal.

Cell-level toxicity is well characterised and unflattering. CC50 on murine T lymphocytes was 24.3 µM at 48 hours ^{4Reference 4Sülsen V et al. · 2011In vitroIn vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifoliaView study →}; on normal human MRC-5 lung fibroblasts, selectivity over the tumour line was only about five-fold ^{10Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}; and in murine lymphoma the authors ranked psilostachyin as more toxic and less active than psilostachyin C ^{11Reference 11Martino R et al. · 2015In vitroSesquiterpene lactones from Ambrosia spp. are active against a murine lymphoma cell line by inducing apoptosis and cell cycle arrest — in vitroView study →}. Its molluscicidal LC50 of 15.9 mg/L against a snail ^{12Reference 12Ding W et al. · 2018Ambrosia artemisiifolia as a potential resource for management of golden apple snails, Pomacea canaliculata (Lamarck)View study →} rounds out a picture of broad, non-specific cytotoxicity.

Mechanistic basis for the caution. Sesquiterpene lactones with an exocyclic methylene conjugated to the lactone carbonyl alkylate nucleophilic groups on enzymes; the checkpoint work showed directly that removing psilostachyin’s α,β-unsaturated carbonyl abolishes its activity ^{9Reference 9Sturgeon CM et al. · 2005In vitroModulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia — in vitroView study →}, and the parasite work showed the effect is competed away by glutathione ^{3,8Reference 3Sülsen V et al. · 2010In vitroAntiproliferative effect and ultrastructural alterations induced by psilostachyin on Trypanosoma cruzi — in vitroView study →Reference 8Barrera P et al. · 2013In vitroNatural sesquiterpene lactones induce oxidative stress in Leishmania mexicana — in vitroView study →}. Depletion of cellular glutathione is a plausible general mechanism of harm at sufficient exposure, though this has been demonstrated in parasites, not in mammalian tissue.

Contact allergy. The sesquiterpene-lactone mix — alantolactone, costunolide and dehydrocostus lactone — sits in the European and North American baseline patch-test series precisely because α-methylene lactones are the principal allergens of the Compositae family, with roughly 1% (Europe) and 0.8% (North America) positivity ^{19Reference 19Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspectsView study →}. Psilostachyin has never been included in a patch-test series, but nothing about its structure suggests it would behave differently from the mix components. This is a type IV, hapten-driven risk and has no relationship to ragweed pollen allergy, which is an IgE response to the protein Amb a 1 and its cross-reactive relatives ^{20Reference 20Zbîrcea LE et al. · 2023Clinical trialRelationship between IgE levels specific for ragweed pollen extract, Amb a 1 and cross-reactive allergen molecules — in patientsView study →}.

Interactions. No CYP450 isoform, P-glycoprotein or other transporter has been tested against psilostachyin. The one transporter datum is negative in a different sense: it does not inhibit the ABCB1 efflux pump in the multidrug-resistance assay where it was screened ^{10Reference 10Kovács B et al. · 2022In vitroAntiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines — in vitroView study →}. A glutathione-depleting electrophile would, in principle, be expected to interact with anything dependent on glutathione conjugation, but this has never been examined.

Reproductive note (prose only). No reproductive or developmental toxicity study of isolated psilostachyin exists. Pregnancy and lactation decisions belong to the herb or product page where intake is decided, not to a molecule page; note separately that mugwort the herb carries a well-established emmenagogue and pregnancy caution which belongs to that page and is not a finding about this molecule.

A citation warning. A 2019 Medical Science Monitor paper reporting anticancer action of psilostachyin-A in 5-fluorouracil-resistant human liver carcinoma was retracted in 2021 following the identification of non-original and manipulated figures ^{22Reference 22Medical Science Monitor editorial office · 2021Retracted: Anticancer action of psilostachyin-A in 5-fluorouracil-resistant human liver carcinoma are mediated through autophagy induction, G2/M phase cell cycle arrest and inhibiting ERK/MAPK signaling pathwayView study →}. It still circulates in secondary literature and should not be used as evidence for anything.

Dosage

There is no human dose for psilostachyin, and no basis on which to construct one. It is not sold as a supplement, is not a medicine anywhere, and has no confirmed source among the herbs here. The figures below are research values, given so the scale of the published work is visible — not as guidance.

Two things make even these numbers hard to use. There are no pharmacokinetics, so no in-vitro concentration can be tied to an achievable plasma level; and the two mouse studies disagree on whether it works in vivo at all ^{2,6Reference 2Sülsen VP et al. · 2008In vitroTrypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in miceView study →Reference 6da Silva CF et al. · 2013In vitroActivities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected miceView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Mabry TJ, Miller HE, Kagan HB, Renold W (1966). The structure of psilostachyin, a new sesquiterpene dilactone from Ambrosia psilostachya. Tetrahedron, 22, 1139–1146. https://doi.org/10.1016/0040-4020(66)80090-X
2. Sülsen VP, Frank FM, Cazorla SI, Anesini CA, Malchiodi EL, Freixa B, Vila R, Muschietti LV, Martino VS (2008). Trypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae) — in vitro and in mice. Antimicrobial Agents and Chemotherapy. https://pubmed.ncbi.nlm.nih.gov/18443111/
3. Sülsen V, Barrera P, Muschietti L, Martino V, Sosa M (2010). Antiproliferative effect and ultrastructural alterations induced by psilostachyin on Trypanosoma cruzi — in vitro. Molecules. https://pubmed.ncbi.nlm.nih.gov/20110908/
4. Sülsen V, Gutierrez Yappu D, Laurella L, Anesini C, Gimenez Turba A, Martino V, Muschietti L (2011). In vitro antiplasmodial activity of sesquiterpene lactones from Ambrosia tenuifolia. Evidence-Based Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/21716685/
5. Sülsen VP, Cazorla SI, Frank FM, Laurella LC, Muschietti LV, Catalán CA, Martino VS, Malchiodi EL (2013). Natural terpenoids from Ambrosia species are active in vitro and in vivo against human pathogenic trypanosomatids. PLoS Neglected Tropical Diseases. https://pubmed.ncbi.nlm.nih.gov/24130916/
6. da Silva CF, Batista DGJ, De Araújo JS, Batista MM, Lionel J, de Souza EM, Hammer ER, da Silva PB, De Mieri M, Adams M, Zimmermann S, Hamburger M, Brun R, Schühly W, Soeiro MNC (2013). Activities of psilostachyin A and cynaropicrin against Trypanosoma cruzi in vitro and in infected mice. Antimicrobial Agents and Chemotherapy. https://pubmed.ncbi.nlm.nih.gov/23939901/
7. Sülsen VP, Puente V, Papademetrio D, Batlle A, Martino VS, Frank FM, Lombardo ME (2016). Mode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on Trypanosoma cruzi — in vitro. PLoS ONE. https://pubmed.ncbi.nlm.nih.gov/26939119/
8. Barrera P, Sülsen VP, Lozano E, Rivera M, Beer MF, Tonn C, Martino VS, Sosa MA (2013). Natural sesquiterpene lactones induce oxidative stress in Leishmania mexicana — in vitro. Evidence-Based Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/23861697/
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11. Martino R, Beer MF, Elso O, Donadel O, Sülsen V, Anesini C (2015). Sesquiterpene lactones from Ambrosia spp. are active against a murine lymphoma cell line by inducing apoptosis and cell cycle arrest — in vitro. Toxicology in Vitro. https://pubmed.ncbi.nlm.nih.gov/26086122/
12. Ding W, Huang R, Zhou Z, He H, Li Y (2018). Ambrosia artemisiifolia as a potential resource for management of golden apple snails, Pomacea canaliculata (Lamarck). Pest Management Science. https://pubmed.ncbi.nlm.nih.gov/29148613/
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14. Guillen E, Terrones H, de Terrones TC, Simirgiotis MJ, Hájek J, Cheel J, Sepulveda B, Areche C (2024). Microwave-assisted extraction of secondary metabolites using ethyl lactate green solvent from Ambrosia arborescens: LC/ESI-MS/MS and antioxidant activity. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/38732429/
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18. Ekiert H, Pajor J, Klin P, Rzepiela A, Ślesak H, Szopa A (2020). Significance of Artemisia vulgaris L. (common mugwort) in the history of medicine and its possible contemporary applications substantiated by phytochemical and pharmacological studies — review. Molecules. https://pubmed.ncbi.nlm.nih.gov/32992959/
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20. Zbîrcea LE, Buzan MR, Grijincu M, Babaev E, Stolz F, Valenta R, Păunescu V, Panaitescu C, Chen KW (2023). Relationship between IgE levels specific for ragweed pollen extract, Amb a 1 and cross-reactive allergen molecules — in patients. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/36835455/
21. Csupor-Löffler B, Hajdú Z, Zupkó I, Réthy B, Falkay G, Forgo P, Hohmann J (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/
22. Medical Science Monitor editorial office (2021). Retracted: Anticancer action of psilostachyin-A in 5-fluorouracil-resistant human liver carcinoma are mediated through autophagy induction, G2/M phase cell cycle arrest and inhibiting ERK/MAPK signaling pathway. Medical Science Monitor. https://pubmed.ncbi.nlm.nih.gov/33762569/
23. Li C, Tu S, Wen S, Li S, Chang J, Shao F, Lei X (2011). Total synthesis of the G2/M DNA damage checkpoint inhibitor psilostachyin C. The Journal of Organic Chemistry. https://pubmed.ncbi.nlm.nih.gov/21417227/
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