Chelidonine

Chelidonine at a Glance

Chelidonine is the principal alkaloid of greater celandine (Chelidonium majus) and the molecule the plant is named for. Structurally it is a benzophenanthridine, like sanguinarine and chelerythrine — but unlike those two it is a tertiary, uncharged alkaloid rather than a quaternary iminium salt, and that single difference drives most of what makes its pharmacology and its toxicology different from theirs.

Its clearest, best-replicated activity is antimitotic. Chelidonine binds tubulin, inhibits its polymerisation, collapses the microtubule network in living cells and arrests them in G2/M — a spindle-poison mechanism confirmed independently in purified-tubulin assays, in cancer cell lines and in whole animals ^{1,2,3,4,5Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →Reference 5Havelek R et al. · 2016In vitroComparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L., against human leukemic and lung carcinoma cells — in vitroView study →}. Alongside that it has a papaverine-like musculotropic spasmolytic action on smooth muscle ^{15Reference 15Hiller KO et al. · 1998Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and Chelidonium majus extracts on isolated guinea-pig ileum — ex vivo/animalView study →}, and a reasonably consistent anti-inflammatory profile through TLR4/NF-κB suppression in rodent models ^{17,18,19Reference 17Liao W et al. · 2018In vitroChelidonine suppresses LPS-induced production of inflammatory mediators through inhibition of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages — in vitro/animalView study →Reference 18Kim SH et al. · 2015AnimalChelidonine, a principal isoquinoline alkaloid of Chelidonium majus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice — animalView study →Reference 19Li M et al. · 2023AnimalChelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats — animalView study →}.

The two things most often said about chelidonine, however, are the two that need the most care. It is repeatedly described as hepatoprotective on the strength of rodent studies ^{7,8Reference 7Paul A et al. · 2013AnimalPoly(lactide-co-glycolide) nano-encapsulation of chelidonine, an active bioingredient of greater celandine, enhances its ameliorative potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →Reference 8Biswas SJ et al. · 2008AnimalEfficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animalView study →} — while the herb it comes from is one of the best-documented herbal causes of acute liver injury in humans ^{27,28,29,30Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 28Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 29Ciornolutchii V et al. · 2024Case reportA hidden cause of hypertransaminasemia: liver toxicity caused by Chelidonium majus L. — report of two cases of herb-induced liver injury and literature review; case seriesView study →Reference 30Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →}. And it is the parent of Ukrain, a semi-synthetic “anticancer drug” whose composition and clinical evidence both fail scrutiny ^{23,24Reference 23Jesionek W et al. · 2016In vitroInvestigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques — in vitroView study →Reference 24Ernst E · 2005Systematic reviewUkrain — a new cancer cure? A systematic review of randomised clinical trialsView study →}. Both stories get their own section below, because getting them wrong is the main way this molecule is misrepresented.

Chelidonine as a Mitotic Inhibitor

This is the section only chelidonine needs, and it is the one mechanism where the evidence is unambiguous. Chelidonine is a genuine spindle poison — not a vague “anticancer natural product,” but a tubulin-binding antimitotic with a defined binding behaviour and a reproducible cellular endpoint.

It binds tubulin at (or near) the colchicine site. In purified rat-brain tubulin, chelidonine, sanguinarine and chelerythrine all inhibit taxol-mediated polymerisation in the micromolar range, but they do it differently: chelidonine is a weak, competitive inhibitor of colchicine binding and does not inhibit podophyllotoxin binding, whereas sanguinarine and chelerythrine inhibit both, by mixed-type kinetics ^{2Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →}. The authors made the mechanistic point explicitly — sanguinarine forms an acid-reversible pseudobase adduct with tubulin through its iminium ion, and chelidonine cannot form that adduct at all, so it must act by a different mechanism ^{2Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →}. That is the molecular reason chelidonine is not simply “a weaker sanguinarine.”

The potency figures, from two independent labs:

Assay	Finding
Tubulin polymerisation (cell-free)	IC50 24 µM 1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →
Tubulin polymerisation (cell-free, +MAPs)	IC50 34.5 ± 9.5 µM 3Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →
G2/M arrest in HeLa cells	88.3% of cells in G2/M at just 2.5 µM 3Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →
Microtubule network in living cells	Depolymerised (HeLa, U2OS); actin-filament mass also reduced 3Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →

The gap between those two numbers is the interesting part. Chelidonine needs tens of micromolar to visibly slow tubulin in a test tube but arrests almost a whole cell population at 2.5 µM — a far stronger cellular effect than sanguinarine or chelerythrine achieved, neither of which arrested the cell cycle at all in the same experiment despite inhibiting tubulin polymerisation more potently ^{3Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →}. Whatever the reason (intracellular accumulation, a different tubulin isotype preference), chelidonine is the cell-cycle-arresting member of the trio, and its relatives are the generally cytotoxic ones.

The arrest is real and it happens in whole organisms. In leukemic T-cell lines and A549 lung carcinoma, chelidonine produced G2/M arrest, Chk1/Chk2 activation, loss of mitochondrial membrane potential and caspase-3/7/8/9 activation, with fluorescence microscopy confirming inhibited tubulin polymerisation inside the cells ^{5Reference 5Havelek R et al. · 2016In vitroComparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L., against human leukemic and lung carcinoma cells — in vitroView study →}. In planarian flatworms — chosen because they are a live readout of pluripotent stem-cell dynamics — chelidonine dose-dependently suppressed stem-cell proliferation, produced mitotic abnormalities, and significantly reduced the number of cells able to progress from metaphase to anaphase/telophase ^{4Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →}. That is a textbook antimitotic phenotype, observed in vivo.

What it is not. Panzer and colleagues, testing chelidonine across two normal, two transformed and two malignant cell lines, found it a weak growth inhibitor with no evidence of selective toxicity for malignant cells ^{1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →}. A spindle poison that does not discriminate between normal and cancerous dividing cells is a toxicology finding as much as a therapeutic one — and it is the honest frame for the “chelidonine kills cancer cells” literature. Its G2/M arrest also runs with activation of the SAPK/JNK stress pathway in every line tested ^{1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →}.

The Hepatoprotective–Hepatotoxic Paradox

This is the safety-critical part of the page, and it cannot be resolved by picking the flattering half. Two bodies of evidence point in opposite directions, and both are real.

What the rodent studies show. Chelidonine, especially as a PLGA nanoformulation, protected mouse liver against cadmium-induced injury: it lowered lipid peroxidation, restored glutathione, SOD, catalase and glutathione reductase, normalised ALT/AST/ALP and improved liver histology ^{7Reference 7Paul A et al. · 2013AnimalPoly(lactide-co-glycolide) nano-encapsulation of chelidonine, an active bioingredient of greater celandine, enhances its ameliorative potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →}. A whole-plant C. majus ethanolic extract reduced chemically induced hepatocarcinogenesis in mice across cytogenetic, biochemical and histological endpoints ^{8Reference 8Biswas SJ et al. · 2008AnimalEfficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animalView study →}. Read alone, this is a coherent antioxidant/hepatoprotective story.

What the human record shows. Greater celandine is a documented cause of idiosyncratic, hepatocellular herb-induced liver injury — causality-assessed case series and reviews describe jaundice with transaminases often above 1,000 IU/L, female predominance, latency of roughly 4–8 weeks and recovery on withdrawal ^{27,28,29,30Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 28Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 29Ciornolutchii V et al. · 2024Case reportA hidden cause of hypertransaminasemia: liver toxicity caused by Chelidonium majus L. — report of two cases of herb-induced liver injury and literature review; case seriesView study →Reference 30Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →}. It is not dose-predictable, and has been reported at ordinary intakes. The EMA’s Committee on Herbal Medicinal Products declined a traditional-use registration on those safety grounds ^{32Reference 32European Medicines Agency · 2011ReviewAssessment report on Chelidonium majus L., herba (EMA/HMPC/369801/2009) — monograph. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-chelidonium-majus-l-herba_en.pdfView study →}.

These are not the same statement about the same substance, and here is why that matters.

• The clinical injury is reported for the herb, not the isolate. There is no case series of chelidonine-induced hepatitis. Every published case involves a Chelidonium preparation — capsules, extracts, tea — of unstated and highly variable alkaloid composition ^{27,28,29Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 28Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 29Ciornolutchii V et al. · 2024Case reportA hidden cause of hypertransaminasemia: liver toxicity caused by Chelidonium majus L. — report of two cases of herb-induced liver injury and literature review; case seriesView study →}.
• When the alkaloids are ranked head-to-head, chelidonine is near the bottom. In cultured rat hepatocytes the cationic congeners were the toxic ones: rank order coptisine > chelerythrine > sanguinarine > chelidonine > protopine > dihydrosanguinarine, with the cationic three at EC20 values ≤2 µM and the neutral ones — chelidonine among them — markedly less toxic ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}. Lipophilicity analysis pinned the difference on the charged, polar congeners.
• A second, independent method reached the same verdict. Screening which C. majus alkaloids actually accumulate inside human HL-7702 liver cells, and pairing that with viability, identified sanguinarine, coptisine and chelerythrine — not chelidonine — as the main hepatotoxic constituents ^{10Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →}.
• Chelidonine is also the non-genotoxic one. In a direct comparison, sanguinarine and chelerythrine produced dose-dependent DNA damage in primary mouse spleen cells and leukemic cells, while chelidonine did not damage DNA ^{11Reference 11Kaminskyy V et al. · 2008In vitroDifferential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells — in vitroView study →}.
• But “less toxic than sanguinarine” is not “safe.” Chelidonine is cytotoxic to hepatocytes at higher exposures ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}, it is directly cytotoxic to HepG2 liver cells ^{6Reference 6Paul A et al. · 2013In vitroCytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo — in vitro/animalView study →}, and it is metabolically activated in the liver — human liver microsomes and rat bile both yield catechol and dicatechol metabolites that go on to form five glutathione conjugates, evidence of bioactivation to reactive ortho-quinones, via CYP3A4, 1A2, 2C19 and 2D6 ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}. Reactive-metabolite formation is exactly the kind of mechanism that underlies idiosyncratic, non-dose-dependent liver injury.

Where that leaves the tension. The most defensible reading is that hepatoprotective and hepatotoxic describe different exposures rather than contradicting each other: at low exposures in a toxin-challenged rodent, chelidonine’s antioxidant and anti-inflammatory effects dominate ^{7Reference 7Paul A et al. · 2013AnimalPoly(lactide-co-glycolide) nano-encapsulation of chelidonine, an active bioingredient of greater celandine, enhances its ameliorative potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →}; at higher exposures the same molecule kills hepatocytes ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →} and generates reactive metabolites in human liver enzymes ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}. Meanwhile the human injury signal is a herb-level phenomenon that the isolate-level data assign mainly to chelidonine’s cationic co-alkaloids ^{9,10Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →}.

Two further facts belong here. Whole C. majus was not hepatotoxic in a 4-week Wistar-rat feeding study ^{31Reference 31Mazzanti G et al. · 2009AnimalChelidonium majus is not hepatotoxic in Wistar rats, in a 4-week feeding experiment — animalView study →} — which is precisely why the human injury is read as idiosyncratic rather than as simple dose-dependent toxicity, and why animal safety data give no reassurance. And the toxicological comparison itself found that reported liver alkaloid levels in experimental animals were too low to reach the cytotoxic concentrations, probably because of very poor oral availability ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →} — an important caveat that cuts against reading any in-vitro EC20 as a human risk threshold. The EU has nonetheless set a safe oral limit of no more than 2.5 mg total C. majus alkaloids per day ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}.

⚠️ Practical bottom line: “chelidonine is hepatoprotective in mice” is a true sentence that must never be used to imply greater celandine is liver-safe. The herb’s documented risk stands regardless of what its principal alkaloid does in a cadmium model.

The Ukrain Story

Ukrain (NSC-631570) is the reason many people have heard of chelidonine at all. It was marketed from the 1970s onward as a semi-synthetic thiophosphoric-acid derivative of chelidonine — specifically, a tris-aziridide conjugate claimed to be selectively toxic to malignant cells while sparing normal ones. It is worth stating its evidential position plainly, because the promotional literature around it is large.

The composition claim does not survive analysis. When Ukrain was subjected to TLC and LC-MS/MS and compared against a plain C. majus root alkaloid extract, what was found was a mixture of the plant’s own alkaloids — chelidonine, sanguinarine, chelerythrine, protopine, allocryptopine, homochelidonine, berberine and coptisine, plus stylopine, norchelidonine, dihydrochelidonine and hydroberberine reported for the first time ^{23Reference 23Jesionek W et al. · 2016In vitroInvestigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques — in vitroView study →}. Two decades earlier, researchers working on chelidonine had already noted that they came to the molecule because chelidonine is a major contaminant of Ukrain ^{1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →}. The honest description is: a Chelidonium alkaloid preparation whose claimed single-entity thiophosphoric structure is not what the analytical chemistry shows.

The clinical evidence. A systematic review of the randomised trials found seven RCTs, all reporting curative effects across a range of cancers — and judged the methodological quality of most of them poor, with the interpretation of several further impeded by other problems; the conclusion was that “numerous caveats prevent a positive conclusion, and independent rigorous studies are urgently needed” ^{24Reference 24Ernst E · 2005Systematic reviewUkrain — a new cancer cure? A systematic review of randomised clinical trialsView study →}. The most-cited individual result, a phase II randomised trial in unresectable pancreatic cancer, reported a survival advantage for Ukrain with or without gemcitabine ^{25Reference 25Gansauge F et al. · 2002RCTNSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer: results of a phase II randomised clinical trialView study →}. No independent replication followed, and the product has never been approved as a medicine in any major regulator’s market ^{32,34Reference 32European Medicines Agency · 2011ReviewAssessment report on Chelidonium majus L., herba (EMA/HMPC/369801/2009) — monograph. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-chelidonium-majus-l-herba_en.pdfView study →Reference 34Zielińska S et al. · 2018ReviewGreater celandine’s ups and downs — 21 centuries of medicinal uses of Chelidonium majus from the viewpoint of today’s pharmacology; reviewView study →}.

A note on retractions. As of July 2026 no Ukrain trial indexed in PubMed carries a retraction notice or an expression of concern. The problem with this literature is not formal retraction — it is that the trials are small, methodologically weak, overwhelmingly from a narrow group of investigators, and never independently reproduced ^{24Reference 24Ernst E · 2005Systematic reviewUkrain — a new cancer cure? A systematic review of randomised clinical trialsView study →}.

The one head-to-head result is not flattering. In a highly metastatic murine pancreatic model, a defatted C. majus extract at 1.2 mg/kg significantly reduced metastasis counts, while Ukrain at 3.6 mg/kg did not ^{26Reference 26Capistrano I R et al. · 2015In vitroIn vitro and in vivo investigations on the antitumour activity of Chelidonium majus — in vitro/animalView study →}. Whatever activity the preparation has, it did not outperform the plain plant extract in that experiment.

What this means for the compound page. Ukrain data are not chelidonine data and are not greater celandine data. They belong to a proprietary preparation of uncertain composition and should not be imported into either — a point the herb-side extraction notes for this plant make explicitly.

What It's Used For

Chelidonine’s evidence base is entirely preclinical: purified-enzyme, cell-line, ex-vivo tissue and rodent work on the isolated alkaloid, plus a large body of whole-plant research where its specific contribution is inferred rather than measured. There are no human efficacy trials of chelidonine.

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. Chelidonine has no human efficacy trials, so every score is capped low and reflects preclinical mechanism only. Each application links down to its write-up.

01Antimitotic & AnticancerShaky40%Replicated tubulin binding + G2/M arrest across cell-free, cell-line and whole-animal systems — but non-selective and with no in-vivo tumour efficacy ^{1,2,3,4,5Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →Reference 5Havelek R et al. · 2016In vitroComparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L., against human leukemic and lung carcinoma cells — in vitroView study →}

02Anti-InflammatoryShaky38%Isolate TLR4/NF-κB mechanism plus three independent rodent models (LPS, asthma, osteoarthritis) ^{17,18,19Reference 17Liao W et al. · 2018In vitroChelidonine suppresses LPS-induced production of inflammatory mediators through inhibition of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages — in vitro/animalView study →Reference 18Kim SH et al. · 2015AnimalChelidonine, a principal isoquinoline alkaloid of Chelidonium majus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice — animalView study →Reference 19Li M et al. · 2023AnimalChelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats — animalView study →}

03Spasmolytic (Smooth Muscle)Shaky32%Ex-vivo guinea-pig ileum with a defined papaverine-like musculotropic mechanism; no human data ^{15Reference 15Hiller KO et al. · 1998Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and Chelidonium majus extracts on isolated guinea-pig ileum — ex vivo/animalView study →}

04Hepatoprotective (Rodent)Shaky28%Two rodent models, one of them a nanoformulation — directly contradicted by the source herb’s clinical record ^{7,8,27Reference 7Paul A et al. · 2013AnimalPoly(lactide-co-glycolide) nano-encapsulation of chelidonine, an active bioingredient of greater celandine, enhances its ameliorative potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →Reference 8Biswas SJ et al. · 2008AnimalEfficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animalView study →Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →}

05Antimicrobial & AntifungalShaky20%One antifungal EC50 against a plant pathogen; consistently weaker than its co-alkaloids ^{21,23Reference 21Pan J et al. · 2017In vitroEnrichment of chelidonine from Chelidonium majus L. using macroporous resin and its antifungal activity — in vitroView study →Reference 23Jesionek W et al. · 2016In vitroInvestigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques — in vitroView study →}

06AnalgesicShaky12%Traditional attribution only; the one dedicated CNS screen found antinociception in derivatives but not in chelidonine itself ^{20Reference 20Grynkiewicz G et al. · 2001Synthesis and biological activity of O-acyl and O-alkyl chelidonine derivatives — animalView study →}

Mechanisms

The load-bearing point: chelidonine’s mechanism set is a tubulin/NF-κB one. The DNA-intercalating, iminium-driven reactivity that defines sanguinarine and chelerythrine is absent here — chelidonine is uncharged and cannot form the pseudobase adduct at all ^{2,11,16Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →Reference 11Kaminskyy V et al. · 2008In vitroDifferential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells — in vitroView study →Reference 16Vavrečková C et al. · 1996In vitroBenzophenanthridine alkaloids of Chelidonium majus; IView study →}.

Pharmacokinetics

There is no human pharmacokinetic dataset for chelidonine, and the animal picture is dominated by one finding: oral bioavailability is poor. Investigators developing a nanoformulation stated the problem plainly — “poor oral bioavailability of chelidonine … makes its optimal use rather limited” — and demonstrated that PLGA encapsulation produced higher systemic availability, better tissue distribution and, unlike free chelidonine, penetration into brain tissue; free chelidonine did not ^{6Reference 6Paul A et al. · 2013In vitroCytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo — in vitro/animalView study →}. A validated LC-MS/MS method quantifying chelidonine alongside protopine, coptisine, sanguinarine and chelerythrine in rat plasma after intragastric C. majus extract confirms that the alkaloid is absorbed and measurable, but at nanogram-per-millilitre sensitivity (LLOQ 0.197–1.27 ng/mL) ^{14Reference 14Zhou Q et al. · 2013AnimalA sensitive and selective LC-MS/MS method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. in rat plasma and its application to a pharmacokinetic study — animalView study →}.

The toxicological consequence is important and works in the reader’s favour: comparing cytotoxic concentrations against reported liver alkaloid levels in dosed animals, one group concluded the achieved liver levels were too low to cause hepatotoxicity, probably because of extremely low oral availability of certain C. majus alkaloids ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}. Practical reading: the micromolar potencies quoted throughout are in-vitro concentrations that oral greater celandine is unlikely to reach systemically — which cuts against both the therapeutic claims and the direct-toxicity claims made for the isolate.

Metabolically, chelidonine is oxidised by CYP3A4, 1A2, 2C19 and 2D6 to two catechol isomers and a dicatechol, all three of which form glutathione conjugates — the signature of bioactivation to electrophilic ortho-quinones, confirmed in both human liver microsomes and rat bile ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}. No half-life, Cmax or absolute bioavailability figure for isolated chelidonine in humans was identified.

Clinical Trials

There are no clinical trials of chelidonine as an isolated compound. The human trial literature adjacent to this molecule belongs to Ukrain (NSC-631570), a Chelidonium alkaloid preparation of disputed composition whose randomised trials were judged methodologically poor and never independently replicated ^{23,24,25Reference 23Jesionek W et al. · 2016In vitroInvestigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques — in vitroView study →Reference 24Ernst E · 2005Systematic reviewUkrain — a new cancer cure? A systematic review of randomised clinical trialsView study →Reference 25Gansauge F et al. · 2002RCTNSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer: results of a phase II randomised clinical trialView study →}. The only controlled human data for the source herb tested a Chelidonium–turmeric combination product, from which no chelidonine-specific conclusion can be drawn.

Last checked: July 2026.

Isolate vs. Plant Studies

Chelidonine sits at an unusual point on this axis: the mechanistic literature is almost all isolate work, while the human record is entirely plant-level — and the two do not meet.

Isolate side. Every tubulin, cell-cycle, CYP and reactive-metabolite result above used purified chelidonine ^{1,2,3,4,5,12,13Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →Reference 5Havelek R et al. · 2016In vitroComparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L., against human leukemic and lung carcinoma cells — in vitroView study →Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →Reference 13Liu Y et al. · 2019In vitroMechanism-based inactivation of cytochrome P450 2D6 by chelidonine — in vitroView study →}. The rodent anti-inflammatory models dosed the isolate ^{17,18,19Reference 17Liao W et al. · 2018In vitroChelidonine suppresses LPS-induced production of inflammatory mediators through inhibition of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages — in vitro/animalView study →Reference 18Kim SH et al. · 2015AnimalChelidonine, a principal isoquinoline alkaloid of Chelidonium majus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice — animalView study →Reference 19Li M et al. · 2023AnimalChelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats — animalView study →}, as did the cadmium-hepatoprotection study ^{7Reference 7Paul A et al. · 2013AnimalPoly(lactide-co-glycolide) nano-encapsulation of chelidonine, an active bioingredient of greater celandine, enhances its ameliorative potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →}. The comparative toxicology that ranks the C. majus alkaloids against each other is also isolate work, and it is the most useful evidence here for attributing effects correctly ^{9,10,11Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →Reference 11Kaminskyy V et al. · 2008In vitroDifferential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells — in vitroView study →}.

Plant side. The hepatocarcinogenesis protection ^{8Reference 8Biswas SJ et al. · 2008AnimalEfficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animalView study →}, the choleretic and antimicrobial traditions, and — critically — all of the human liver-injury cases ^{27,28,29,30Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 28Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 29Ciornolutchii V et al. · 2024Case reportA hidden cause of hypertransaminasemia: liver toxicity caused by Chelidonium majus L. — report of two cases of herb-induced liver injury and literature review; case seriesView study →Reference 30Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →} are whole-herb findings. Attribution to chelidonine specifically is inference, and the two studies that tried to make that attribution empirically both concluded the main hepatotoxic constituents are chelidonine’s cationic relatives, not chelidonine ^{9,10Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →}.

The transfer caveat that matters most here is compositional. Greater celandine’s alkaloid profile is not stable. Total alkaloids run roughly 0.27–2.25% in aerial parts and 3–4% in root ^{33Reference 33Li XL et al. · 2024ReviewAlkaloids in Chelidonium majus L: a review of its phytochemistry, pharmacology and toxicology — reviewView study →}, root and latex are far richer than the herb, and the benzophenanthridines together make up on the order of a fifth of fresh latex ^{36Reference 36Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings; reviewView study →}. Cultivation itself shifts the profile: in one controlled comparison, wild-grown plants were coptisine-dominant while cultivated plants of the same population became chelidonine-dominant, with higher total alkaloid content and higher cytotoxicity ^{35Reference 35Krizhanovska V et al. · 2021In vitroThe cultivation of Chelidonium majus L. increased the total alkaloid content and cytotoxic activity compared with those of wild-grown plants — in vitroView study →}. A “greater celandine” product can therefore deliver very different chelidonine exposures depending on part, provenance and growing conditions — which is one reason herb-level findings and molecule-level findings should not be swapped for each other.

Prevalence in Nature

Chelidonine is best understood as a marker alkaloid of greater celandine (Chelidonium majus, Papaveraceae). Unlike sanguinarine and chelerythrine — which are widespread across the poppy and rue families and are commercially extracted from bloodroot and Macleaya — chelidonine is not a broadly distributed phytochemical, and no confirmed occurrence in another genus was established.

Within the plant it follows the family’s laticifer pattern: root and latex are far richer than aerial parts, and total alkaloid content runs roughly 0.27–2.25% of aerial parts and 3–4% of root ^{33Reference 33Li XL et al. · 2024ReviewAlkaloids in Chelidonium majus L: a review of its phytochemistry, pharmacology and toxicology — reviewView study →}. In the one quantified measurement available here, chelidonine was ~1.75 mg/g of a 25% ethanol aerial-part extract — the second most abundant alkaloid measured, behind coptisine (~6.42 mg/g) and well ahead of sanguinarine (~0.22), berberine (~0.11) and chelerythrine (~0.06) ^{22Reference 22Orvos P et al. · 2015In vitroEffects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential — a safety approach; in vitro/animalView study →}. The bright yellow latex is the alkaloid-densest tissue, with the benzophenanthridines plus coptisine reaching around a fifth of fresh latex ^{36Reference 36Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings; reviewView study →}.

It travels with a small family of close congeners in the same plant — homochelidonine (its dimethoxy analogue, which shares its tubulin-inhibiting and G2/M-arresting behaviour but is generally weaker) ^{5Reference 5Havelek R et al. · 2016In vitroComparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L., against human leukemic and lung carcinoma cells — in vitroView study →}, norchelidonine and dihydrochelidonine ^{23Reference 23Jesionek W et al. · 2016In vitroInvestigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques — in vitroView study →} — plus the co-occurring sanguinarine, chelerythrine, coptisine, berberine, protopine, allocryptopine and stylopine.

Absolute content is genuinely variable: it shifts several-fold with plant part, ecotype and season, and — as noted above — cultivation can flip which alkaloid dominates the extract entirely ^{35Reference 35Krizhanovska V et al. · 2021In vitroThe cultivation of Chelidonium majus L. increased the total alkaloid content and cytotoxic activity compared with those of wild-grown plants — in vitroView study →}.

Discovery & Synthesis

Chelidonine is one of the earliest plant alkaloids to be described, isolated from Chelidonium majus and named “chélidonine” in the 1820s, in the first generation of alkaloid chemistry that followed morphine — though sources differ on whether that first preparation was pure chelidonine or an alkaloid fraction, with pure material often credited to work in 1839. Reviews of the plant note simply that its major pharmacologically relevant alkaloids “were first isolated over a century ago” ^{34Reference 34Zielińska S et al. · 2018ReviewGreater celandine’s ups and downs — 21 centuries of medicinal uses of Chelidonium majus from the viewpoint of today’s pharmacology; reviewView study →}. The name traces the plant’s own: Greek chelidṓn, the swallow, from the ancient association between the plant’s flowering and the birds’ return ^{34Reference 34Zielińska S et al. · 2018ReviewGreater celandine’s ups and downs — 21 centuries of medicinal uses of Chelidonium majus from the viewpoint of today’s pharmacology; reviewView study →}.

First total synthesis. Oppolzer and Keller published the total synthesis of dl-chelidonine in 1971 ^{37Reference 37Oppolzer W · 1971Total synthesis of dl-chelidonineView study →}, later refining it into a highly stereoselective intramolecular o-quinodimethane/nitrostyrene cycloaddition route. Chelidonine has remained an attractive synthetic target for its fused hexahydrobenzo[c]phenanthridine core: a concise enantioselective route to (+)-chelidonine alongside (+)-homochelidonine, (+)-chelamidine, (+)-chelamine and (+)-norchelidonine was reported in 2008 via a Pd(II)-catalysed ring-forming step ^{39Reference 39Fleming MJ et al. · 2008Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a Pd(II)-catalysed ring-forming reactionView study →}, and a further total synthesis of chelidonine and norchelidonine using an enamide–benzyne [2+2] cycloaddition cascade in 2012 ^{38Reference 38Ma ZX et al. · 2012Total syntheses of chelidonine and norchelidonine via an enamide-benzyne-[2+2] cycloaddition cascadeView study →}.

Manufacture today is extraction from Chelidonium majus, not synthesis — the syntheses are academic demonstrations rather than production routes. Practical enrichment uses macroporous adsorption resin: D101 resin raised chelidonine content from 2.67% to 37.81% of the extract, a 14-fold enrichment at ~81% recovery, which is the kind of low-cost process actually used to obtain gram quantities ^{21Reference 21Pan J et al. · 2017In vitroEnrichment of chelidonine from Chelidonium majus L. using macroporous resin and its antifungal activity — in vitroView study →}. Reagent- and reference-grade chelidonine is sold as the free base or hydrochloride.

Patents: not yet researched.

Toxicity & Safety

Chelidonine carries a [moderate] flag. That is a deliberate middle call and it deserves its reasoning stated openly.

Why not “low”: it is a genuine spindle poison with no selectivity for malignant over normal dividing cells ^{1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →}, demonstrated in vivo to suppress proliferating stem cells and produce mitotic abnormalities ^{4Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →}; it is bioactivated by human liver enzymes to reactive ortho-quinones ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}; and it is a mechanism-based (irreversible) inactivator of CYP2D6 ^{13Reference 13Liu Y et al. · 2019In vitroMechanism-based inactivation of cytochrome P450 2D6 by chelidonine — in vitroView study →}, a real drug-interaction liability. It is also cytotoxic to hepatocytes at higher exposures ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}.

Why not “toxic” or higher: in every head-to-head comparison it is the less dangerous member of its own family. It ranks below coptisine, chelerythrine and sanguinarine for hepatocyte cytotoxicity ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}; it was not among the constituents identified as the main hepatotoxic components of C. majus ^{10Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →}; it does not damage DNA where its quaternary relatives do ^{11Reference 11Kaminskyy V et al. · 2008In vitroDifferential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells — in vitroView study →}; and it is chemically incapable of the iminium/pseudobase reactivity that drives their cytotoxicity ^{2Reference 2Wolff J · 1993In vitroAntimicrotubule properties of benzophenanthridine alkaloids — in vitroView study →}. There is no case series of chelidonine-induced liver injury — the human cases are for the herb.

Safety at a Glance

⚠️ Moderate toxicity

• The source herb is a documented cause of acute liver injury. Greater celandine causes idiosyncratic hepatocellular hepatitis — jaundice, transaminases often >1,000 IU/L, latency ~4–8 weeks, recovery on withdrawal — and the EMA/HMPC declined a traditional-use registration on those grounds ^{27,28,29,30,32Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 28Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 29Ciornolutchii V et al. · 2024Case reportA hidden cause of hypertransaminasemia: liver toxicity caused by Chelidonium majus L. — report of two cases of herb-induced liver injury and literature review; case seriesView study →Reference 30Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →Reference 32European Medicines Agency · 2011ReviewAssessment report on Chelidonium majus L., herba (EMA/HMPC/369801/2009) — monograph. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-chelidonium-majus-l-herba_en.pdfView study →}. This is the single most important fact on the page, and it applies to anything containing chelidonine.
• Whose toxicity is it? Not clearly chelidonine’s. Two independent isolate-level methods assign the main hepatotoxicity of C. majus to sanguinarine, coptisine and chelerythrine — the cationic alkaloids — with chelidonine ranking lower and causing no DNA damage ^{9,10,11Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →Reference 11Kaminskyy V et al. · 2008In vitroDifferential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells — in vitroView study →}. That is an argument about attribution, not an all-clear: chelidonine is still cytotoxic to hepatocytes at higher exposures ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}.
• Bioactivated to reactive metabolites in the liver. CYP3A4/1A2/2C19/2D6 convert chelidonine to catechols and ortho-quinones that form glutathione conjugates in human microsomes and rat bile ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →} — the classic mechanistic setup for idiosyncratic injury.
• An antimitotic, with everything that implies. Tubulin binding, G2/M arrest and in-vivo suppression of proliferating stem cells ^{1,3,4Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →}, with no selectivity for cancer cells ^{1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →}. Rapidly dividing tissues are the exposed ones.
• Irreversible CYP2D6 inactivation — a real interaction signal. Mechanism-based inactivation (KI 20.49 µM, kinact 11.05 min⁻¹; activity not restored by dialysis) means co-administered CYP2D6 substrates could accumulate ^{13Reference 13Liu Y et al. · 2019In vitroMechanism-based inactivation of cytochrome P450 2D6 by chelidonine — in vitroView study →}; CYP3A4, 1A2 and 2C19 are also involved in its metabolism ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}.
• Alkaloid content varies enormously between preparations. Root and latex far exceed aerial parts, total alkaloids run ~0.27–2.25% (aerial) to 3–4% (root), and cultivation can flip a coptisine-dominant extract into a chelidonine-dominant one ^{33,35Reference 33Li XL et al. · 2024ReviewAlkaloids in Chelidonium majus L: a review of its phytochemistry, pharmacology and toxicology — reviewView study →Reference 35Krizhanovska V et al. · 2021In vitroThe cultivation of Chelidonium majus L. increased the total alkaloid content and cytotoxic activity compared with those of wild-grown plants — in vitroView study →}. “Greater celandine” is not one exposure.
• Cardiac signal for the alkaloid mixture. C. majus extracts and their major alkaloids block hERG potassium channels and prolong the dog cardiac action potential — a QT/arrhythmia caution for concentrated alkaloid exposure ^{22Reference 22Orvos P et al. · 2015In vitroEffects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential — a safety approach; in vitro/animalView study →}.
• Poor oral bioavailability limits real-world exposure. Free chelidonine is poorly absorbed ^{6Reference 6Paul A et al. · 2013In vitroCytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo — in vitro/animalView study →}, and liver levels achieved in dosed animals were judged too low to reach cytotoxic concentrations ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}. This is the main reason the in-vitro numbers should not be read as human risk thresholds — and it undercuts the therapeutic claims equally.
• Not genotoxic in direct comparison. Where sanguinarine and chelerythrine produced dose-dependent DNA damage in primary mouse spleen and leukemic cells, chelidonine did not ^{11Reference 11Kaminskyy V et al. · 2008In vitroDifferential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells — in vitroView study →}.

Full Safety & Interactions Detail

Hepatic. The full argument is in The Hepatoprotective–Hepatotoxic Paradox above; the short version is that greater celandine’s human liver-injury signal is real, well-documented and reason enough to avoid internal use of the herb ^{27,28,29,30,32Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 28Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 29Ciornolutchii V et al. · 2024Case reportA hidden cause of hypertransaminasemia: liver toxicity caused by Chelidonium majus L. — report of two cases of herb-induced liver injury and literature review; case seriesView study →Reference 30Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →Reference 32European Medicines Agency · 2011ReviewAssessment report on Chelidonium majus L., herba (EMA/HMPC/369801/2009) — monograph. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-chelidonium-majus-l-herba_en.pdfView study →}, while the isolate-level evidence points at chelidonine’s cationic co-alkaloids rather than chelidonine as the primary hepatotoxins ^{9,10Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →Reference 10Wu C et al. · 2019In vitroIntracellular accumulation as an indicator of cytotoxicity to screen hepatotoxic components of Chelidonium majus L. by LC-MS/MS — in vitroView study →}. Chelidonine’s own contribution is direct hepatocyte cytotoxicity at higher exposures ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →} plus reactive-metabolite formation ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}. The EU has set an oral limit of no more than 2.5 mg total C. majus alkaloids per day ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}. Note that whole C. majus was not hepatotoxic in a 4-week Wistar-rat feeding experiment ^{31Reference 31Mazzanti G et al. · 2009AnimalChelidonium majus is not hepatotoxic in Wistar rats, in a 4-week feeding experiment — animalView study →} — which is why the human pattern is classified as idiosyncratic, and why animal safety data provide no reassurance here.

Drug interactions — named enzymes. Chelidonine is a mechanism-based inactivator of CYP2D6: time-, concentration- and NADPH-dependent inhibition with KI 20.49 µM and kinact 11.05 min⁻¹, ~76% of activity lost after 9 minutes at 50 µM, not restored by dialysis, partially restored by ferricyanide oxidation, and attenuated by the competitive inhibitor quinidine ^{13Reference 13Liu Y et al. · 2019In vitroMechanism-based inactivation of cytochrome P450 2D6 by chelidonine — in vitroView study →}. Because CYP2D6 handles a large share of commonly used psychiatric, cardiovascular and analgesic drugs, this is the most concrete interaction signal on the page — though whether oral greater celandine achieves the necessary hepatic concentrations is unestablished ^{9Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}. CYP3A4, CYP1A2 and CYP2C19 also metabolise (and are inhibited by the reactive metabolites of) chelidonine ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →}. No human drug-interaction study exists.

Cardiac. Hydroalcoholic C. majus extracts and their major alkaloids block the hERG (IKr) potassium channel and prolong the cardiac action potential in canine tissue — framed by the authors explicitly as a safety concern rather than a therapeutic mechanism ^{22Reference 22Orvos P et al. · 2015In vitroEffects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential — a safety approach; in vitro/animalView study →}. This is an alkaloid-mixture finding; caution is warranted with other QT-prolonging agents for any concentrated-alkaloid exposure.

Antimitotic hazard. A tubulin-binding G2/M blocker with no tumour selectivity ^{1Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →} and demonstrated in-vivo suppression of proliferating stem cells ^{4Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →} is, by mechanism class, a hazard to rapidly dividing tissue. That mechanism class also underlies developmental toxicity for other spindle poisons.

Reproductive and developmental findings (prose only). No dedicated reproductive- or developmental-toxicity study of isolated chelidonine was identified. What can be stated is mechanistic rather than empirical: chelidonine is a non-selective antimitotic that arrests dividing cells in G2/M and suppresses proliferating stem-cell populations in vivo ^{1,3,4Reference 1Panzer A et al. · 2001In vitroThe effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitroView study →Reference 3Wang X et al. · 2016In vitroThe interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitroView study →Reference 4Isolani ME et al. · 2012AnimalThe in vivo effect of chelidonine on the stem cell system of planarians — in vivoView study →}, and it is bioactivated to reactive electrophiles by human liver enzymes ^{12Reference 12Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →} — a mechanism profile that argues for conservative treatment during pregnancy and lactation. That judgement belongs on the greater celandine herb page and on any product page, where intake is actually decided, not on this molecule page. Absence of reproductive data is not evidence of safety.

Populations and scope note. Pre-existing liver disease is a contraindication for the source herb, not merely a caution, given the injury pattern ^{27,32Reference 27Teschke R et al. · 2011Case reportHerbal hepatotoxicity by greater celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 32European Medicines Agency · 2011ReviewAssessment report on Chelidonium majus L., herba (EMA/HMPC/369801/2009) — monograph. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-chelidonium-majus-l-herba_en.pdfView study →}. No repeat-dose toxicology, LD50 or genotoxicity battery for isolated chelidonine in humans was identified; the reassuring findings here (non-genotoxic, low rank on hepatocyte cytotoxicity, poor oral availability) are comparative and preclinical, and none of them licenses deliberate high-dose exposure.

Dosage

There is no established or recommended human dose for chelidonine, and none should be inferred. It has never been sold as a stand-alone medicine. Real-world human exposure is indirect — as the principal alkaloid within a greater celandine preparation whose alkaloid content varies several-fold with plant part, provenance and processing ^{33,35Reference 33Li XL et al. · 2024ReviewAlkaloids in Chelidonium majus L: a review of its phytochemistry, pharmacology and toxicology — reviewView study →Reference 35Krizhanovska V et al. · 2021In vitroThe cultivation of Chelidonium majus L. increased the total alkaloid content and cytotoxic activity compared with those of wild-grown plants — in vitroView study →}.

Every figure in the literature is a research concentration or an animal dose:

The single most useful number for a reader is the last one: the EU’s limit applies to total greater celandine alkaloids, not to chelidonine, and exists because of the herb’s liver-injury record ^{9,32Reference 9Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →Reference 32European Medicines Agency · 2011ReviewAssessment report on Chelidonium majus L., herba (EMA/HMPC/369801/2009) — monograph. https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-chelidonium-majus-l-herba_en.pdfView study →}. These are doses and concentrations studied in research and are not a personal recommendation.

References

1. Panzer A, Joubert AM, Bianchi PC, Hamel E, Seegers JC (2001). The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways — in vitro. European Journal of Cell Biology. https://pubmed.ncbi.nlm.nih.gov/11211931/
2. Wolff J, Knipling L (1993). Antimicrotubule properties of benzophenanthridine alkaloids — in vitro. Biochemistry. https://pubmed.ncbi.nlm.nih.gov/7902132/
3. Wang X, Tanaka M, Krstin S, Peixoto HS, Wink M (2016). The interference of selected cytotoxic alkaloids with the cytoskeleton: an insight into their modes of action — in vitro. Molecules. https://pubmed.ncbi.nlm.nih.gov/27420038/
4. Isolani ME, Pietra D, Balestrini L, et al. (2012). The in vivo effect of chelidonine on the stem cell system of planarians — in vivo. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/22503932/
5. Havelek R, Seifrtova M, Kralovec K, et al. (2016). Comparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L., against human leukemic and lung carcinoma cells — in vitro. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/26969379/
6. Paul A, Das S, Das J, Samadder A, Khuda-Bukhsh AR (2013). Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo — in vitro/animal. Toxicology Letters. https://pubmed.ncbi.nlm.nih.gov/23850776/
7. Paul A, Das J, Das S, Samadder A, Khuda-Bukhsh AR (2013). Poly(lactide-co-glycolide) nano-encapsulation of chelidonine, an active bioingredient of greater celandine, enhances its ameliorative potential against cadmium-induced oxidative stress and hepatic injury in mice — animal. Environmental Toxicology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/24035924/
8. Biswas SJ, Bhattacharjee N, Khuda-Bukhsh AR (2008). Efficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animal. Food and Chemical Toxicology. https://pubmed.ncbi.nlm.nih.gov/18215450/
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