Chelidonium majus · PhytoNexus

01 Identity and provenance

Accepted binomial: Chelidonium majus
Common names: Greater Celandine
Family (APG IV): Papaveraceae
Part used: Herb
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): LiverTox NBK548684 (Greater Celandine) | Moro PA et al. J Ethnopharmacol 2009 (literature review and new case) | Stickel F et al. Scand J Gastroenterol 2003;38:565-8 | VERIFIED 2026 (batch 6) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | INTRINSIC

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Isoquinoline alkaloids	Chelidonine Herb	No analogue in current use. Ukrain, a semi-synthetic thiophosphoric acid conjugate of chelidonine, was investigated for cancer on weak evidence.

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: Traditional antispasmodic for dyspepsia, irritable bowel and biliary complaints; oral use was approved by the German Commission E. Latex applied topically to warts. Evidence of therapeutic benefit is weak, which is the key point when weighing the risk.
Reported adverse effects: IDIOSYNCRATIC HEPATOTOXICITY - the pattern matters more than the incidence. Over a dozen European reports of clinically apparent acute liver injury, typically 1-6 months after starting, with jaundice and marked transaminase rises; presentation and histology resemble acute viral hepatitis. In one series of 10 women (ages 37-67) ALT ran 123-1338 U/L, with marked cholestasis in 5; all recovered in 2-6 months after stopping. ONSET IS INDEPENDENT OF DOSE, so there is no safe-dose reassurance to give. POSITIVE RECHALLENGE documented - a second flare on unintentional re-exposure, which is strong causality evidence. REPORTING-BIAS CAVEAT: reports are almost entirely European, with none from the Americas, and herb-induced liver injury is reported about 2.75 times more often in Europe than Asia. Absence of Indian case reports is not evidence of absence of risk.

04 Interaction matrix

Source column, verbatim: THEORETICAL: additive with other hepatotoxic agents. No well-characterised pharmacokinetic interactions.
Normalised onto 1 canonical drug class below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Hepatotoxic drugs Organ toxicity	3Major	Organ-toxicity additive	curated A	Transaminase elevation, cholestasis, sinusoidal obstruction syndrome, acu…	why ▾
Class mechanism. Pyrrolizidine alkaloids, high-dose anthraquinones, kava constituents and germander-type diterpenes cause hepatocellular or sinusoidal injury that adds to the risk from paracetamol, isoniazid, methotrexate, azoles and statins. Expected Transaminase elevation, cholestasis, sinusoidal obstruction syndrome, acute liver failure. Management Baseline and 4-weekly ALT and bilirubin. Stop the botanical at any transaminase rise above three times the upper reference limit. Onset unspecified Evidence A - human data with a cited source Matched on “hepatotoxic” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Immunosuppressants (ciclosporin, tacrolimus, mycophenolate) Transplant	4Contraindicated	PK-CYP3A4/P-gp + PD-antagonistic	predicted D	Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hy…	why ▾
Chemistry of this pair. Berberine inhibits CYP3A4 and P-glycoprotein, lowers glucose through AMPK activation, and displaces bilirubin from albumin. Class mechanism. These are narrow-therapeutic-index CYP3A4 and P-glycoprotein substrates. Botanical induction collapses trough levels; inhibition causes toxic accumulation. Immunostimulant botanicals separately oppose the therapeutic goal. Expected Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hypertension with inhibitors; autoimmune flare with immunostimulants. Management Treat as contraindicated in transplant recipients. Any exposure requires immediate trough level measurement and transplant team notification. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	predicted D	Toxic accumulation or subtherapeutic failure of the co-prescribed drug, s…	why ▾
Chemistry of this pair. Berberine inhibits CYP3A4 and P-glycoprotein, lowers glucose through AMPK activation, and displaces bilirubin from albumin. Class mechanism. Furanocoumarins, bergamottin, piperine, glabridin and berberine inhibit CYP3A4; hyperforin, andrographolide and several diterpenes induce it through PXR. Because CYP3A4 handles roughly half of marketed drugs, the affected list is broad and the direction is product-specific. Expected Toxic accumulation or subtherapeutic failure of the co-prescribed drug, sometimes fatal for antiarrhythmics, immunosuppressants and oncology agents. Management Screen the full regimen for 3A4 substrates. Where the substrate has a narrow index, avoid rather than monitor. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antidiabetic drugs (insulin, sulfonylureas, biguanides, GLP-1, SGLT2) Endocrine	3Major	PD-additive	predicted D	Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events rep…	why ▾
Chemistry of this pair. Berberine inhibits CYP3A4 and P-glycoprotein, lowers glucose through AMPK activation, and displaces bilirubin from albumin. Class mechanism. Hypoglycaemic botanicals act through insulin secretagogue, insulin-sensitising, alpha-glucosidase-inhibiting or glucose-transport routes. Added to a titrated pharmacological regimen the effects summate rather than plateau. Expected Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events reported with insulin and sulfonylureas. Management Increase self-monitoring frequency for 2 weeks after starting or stopping. Anticipate a downward dose adjustment of insulin or sulfonylurea. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antacids, PPIs and H2 blockers Gastrointestinal	2Moderate	PK-absorption	predicted D	Reduced or erratic absorption of alkaloids; heartburn and reflux from pre…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Gastric pH elevation alters the dissolution and ionisation of alkaloidal and enteric-coated botanical products; menthol- and peppermint-oil products lose their enteric protection at high pH and can be released prematurely. Expected Reduced or erratic absorption of alkaloids; heartburn and reflux from premature release of volatile-oil preparations. Management Separate administration by 2 hours. Avoid non-enteric peppermint oil in reflux disease. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

idiosyncratic hepatotoxicity - Dose-independent onset with posit

06 Confusable material

These entries could be mistaken for this one in trade, in the herbarium, or in a prescription. Powdered material is often indistinguishable, so the check is macroscopic, microscopic and chromatographic rather than nominal.

Alpinia galanga

Greater Galangal

Zingiberaceae

Shares the common name "greater"

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Echinacea purpurea Echinacea	Asteraceae	4	0.31
Tinospora cordifolia Giloy	Menispermaceae	4	0.80
Berberis vulgaris Barberry	Berberidaceae	4	0.80
Coptis chinensis Chinese Goldthread	Ranunculaceae	4	0.80
Stephania tetrandra Han Fang Ji	Menispermaceae	4	0.80
Corydalis yanhusuo Yan Hu Suo	Papaveraceae	4	0.80

10 References and notes

Source column: Benninger J et al. Gastroenterology 1999;117:1234-7 (10 cases)

Benninger J et al. Gastroenterology 1999

Benninger J et al. Gastroenterology 1999 manual

117:1234-7 (10 cases)

manual

BibTeX for all 2 records

@article{BenningerJ1999,
  title = {Benninger J et al. Gastroenterology 1999},
  author = {Benninger J et al.},
  journal = {Gastroenterology},
  year = {1999},
}

@article{anon,
  title = {117:1234-7 (10 cases)},
}

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