Greater Celandine

The name comes from the Greek chelidon, a swallow. Pliny gave it to the plant because it flowers when the swallows arrive in spring and fades when they leave. He also recorded a folk belief that swallows used its juice to clear films from their young’s eyes ^{31,32,34Reference 31Bone K · 2013Principles and Practice of PhytotherapyReference 32Grieve M · 1931A Modern Herbal — Celandine, GreaterView study →Reference 34Kiger · 1997Chelidonium majus Linnaeus — genus and species description, habitat and North American distribution — floraView study →}.

Both the root and the aerial parts carry similar alkaloids, and the aerial parts are strongly preferred ^{31Reference 31Bone K · 2013Principles and Practice of Phytotherapy}.

The internal uses are for the liver and gallbladder: gallbladder disease and stones, jaundice and other liver complaints, and support for elimination through the liver and bowel. It is also given for gastric ulcers and for migraine ^{29,31Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →Reference 31Bone K · 2013Principles and Practice of Phytotherapy}. Grieve records it being taken with aniseed to clear obstructions of the liver and gallbladder ^{32Reference 32Grieve M · 1931A Modern Herbal — Celandine, GreaterView study →}.

Externally, the fresh orange latex is applied directly to warts, ringworm and fungal infections, squeezed from a broken stem onto the lesion ^{29,31Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →Reference 31Bone K · 2013Principles and Practice of Phytotherapy}.

In Chinese practice bai qu cai is given for many of the same digestive and liver complaints as in Europe: gastritis, gastric ulcers, enteritis, jaundice and abdominal pain. It is also used for bronchitis and whooping cough ^{31Reference 31Bone K · 2013Principles and Practice of Phytotherapy}.

Actions

Clears heat, cools and dries ^{29Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}. It moves blood stasis arising from Qi stagnation, relieves pain, promotes urination in oedema, and relieves cough.

Indications

Abdominal pain, peptic ulcers, chronic bronchitis and whooping cough ^{33Reference 33Bone K · 2003A Clinical Guide to Blending Liquid Herbs}. It is particularly indicated for damp-heat patterns, of which congested bile is the clearest example ^{29Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}.

The bitter taste is also thought to influence the heart ^{29Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}.

This is the herb’s traditional core use and the only indication with controlled human data. A placebo-controlled, double-blind multicentre study (n=76, 3 weeks) tested Cholagogum F Nattermann, which combines dried extracts of Chelidonium and Curcuma. It relieved dull and colicky right-upper-quadrant pain from biliary dyskinesia faster than placebo, with no side effects. Secondary digestive symptoms improved equally in both arms ^{1Reference 1Niederau C · 1999RCTThe effect of chelidonium- and turmeric root extract on upper abdominal pain due to functional disorders of the biliary system — a placebo-controlled double-blind randomised studyView study →}.

Because the product combines celandine with turmeric, the trial cannot isolate a celandine effect. A whole-herb extract increased bile flow in the isolated perfused rat liver ^{2Reference 2Vahlensieck U et al. · 1995AnimalThe effect of Chelidonium majus herb extract on choleresis in the isolated perfused rat liver — animalView study →}, and older pharmacological reviews attribute biliary and antispasmodic effects to the protopine- and coptisine-type alkaloids ^{18,29Reference 18Colombo ML · 1996ReviewPharmacological activities of Chelidonium majus L. (Papaveraceae) — reviewView study →Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}.

Gap: stimulating bile flow is the wrong action in obstructive gallstone disease, and gallstones are among the complaints celandine is traditionally given for. There is also no placebo-controlled trial of celandine alone; the one positive human result is confounded by turmeric.

A methanol extract suppressed collagen-induced arthritis in mice. It lowered TNF-α, IL-6 and IFN-γ, reduced B- and γδ-T-cell populations and raised CD4+CD25+ regulatory T cells ^{3Reference 3Lee YC et al. · 2007AnimalSuppressive effects of Chelidonium majus methanol extract on collagen-induced arthritis in mice — animal modelView study →}.

At the molecular level, the benzophenanthridines sanguinarine and chelerythrine are potent, non-redox inhibitors of 5- and 12-lipoxygenase, while chelidonine is inactive there ^{4Reference 4Vavrecková C et al. · 1996In vitroBenzophenanthridine alkaloids of Chelidonium majus; inhibition of 5- and 12-lipoxygenase by a non-redox mechanism — in vitroView study →}. Newer isolates (lignanamides and minor alkaloids) inhibit nitric-oxide production in LPS-stimulated macrophages at low-micromolar IC50 ^{5Reference 5Huang XY et al. · 2019In vitroNew lignanamides and alkaloids from Chelidonium majus and their anti-inflammation activity — in vitroView study →}.

Entirely preclinical, with no human inflammatory endpoint tested. The most active anti-inflammatory alkaloids are the same ones implicated in cytotoxicity.

Rodent work is consistent. An ethanolic whole-plant extract reduced p-dimethylaminoazobenzene–induced hepatocarcinogenesis in mice across cytogenetic, biochemical and histological endpoints ^{6Reference 6Biswas SJ et al. · 2008AnimalEfficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animalView study →}. Chelidonine, especially as a PLGA nanoformulation, protected mouse liver against cadmium-induced oxidative injury, restoring GSH and normalising ALT, AST and ALP ^{7Reference 7Paul A et al. · 2013AnimalPLGA nano-encapsulation of chelidonine enhances its potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →}.

Earlier CCl4 studies cited in reviews point the same direction ^{29Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}.

Gap: the same herb that protects rodent livers is a documented cause of liver injury in people ^{21,22,23,30Reference 21Teschke R et al. · 2011Case reportHerbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 22Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 23Ciornolutchii V et al. · 2024ReviewLiver toxicity caused by Chelidonium majus L.: two cases of herb-induced liver injury and literature reviewView study →Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}, and its isolated alkaloids are directly cytotoxic to hepatocytes at higher exposures ^{25Reference 25Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}. The rodent protection findings do not show that the herb is safe for the human liver.

Across independent screens the alkaloid fraction is active against gram-positive bacteria, including Staphylococcus aureus (MRSA among them) and streptococci, and against biofilms. The activity is attributed largely to sanguinarine and chelerythrine ^{8,9,29Reference 8Zielińska S et al. · 2021In vitroScreening Papaveraceae as novel antibiofilm natural-based agents — in vitroView study →Reference 9Kokoska L et al. · 2002In vitroScreening of some Siberian medicinal plants for antimicrobial activity — in vitroView study →Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}.

A screen of Siberian medicinal plants ranked celandine among the most active ^{9Reference 9Kokoska L et al. · 2002In vitroScreening of some Siberian medicinal plants for antimicrobial activity — in vitroView study →}.

Antifungal activity (Candida, dermatophytes) and antiviral activity (HSV-1, adenovirus, and the plant virus TMV) are reported in cell and assay systems ^{10,29Reference 10Guo W et al. · 2021In vitroAnti-TMV activity and mode of action of three alkaloids isolated from Chelidonium majus — in vitroView study →Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}. This matches the traditional use of the alkaloid-dense latex on warts and skin infections.

All in vitro. Activity tracks alkaloid content and extract type, and no controlled human infection study, topical or systemic, has been done.

There are no human trials of celandine for pain. In rat periaqueductal-grey neurons, Chelidonii herba modulated glycine- and glutamate-activated currents ^{13Reference 13Shin MC et al. · 2003AnimalModulation of Chelidonii herba on glycine-activated and glutamate-activated ion currents in rat periaqueductal grey neurons — animalView study →} and enhanced the GABA-activated chloride current ^{14Reference 14Kim Y et al. · 2001AnimalModulation of Chelidonii herba on GABA-activated chloride current in rat PAG neurons — animalView study →}, pathways involved in pain transmission.

Whole extracts and major alkaloids also block hERG potassium channels and alter cardiac action potentials, a finding the authors framed as a cardiac-safety concern ^{16Reference 16Orvos 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 →}.

Separately, berberine blunted morphine-induced locomotor sensitisation and analgesic tolerance in mice ^{15Reference 15Yoo JH et al. · 2006AnimalInhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice — animalView study →}.

Animal and ex-vivo work only, with no clinical analgesia data. The ion-channel activity that might explain the effect includes hERG block, which is a cardiac risk.

Cell-line data are broad and repeatable. Whole-herb and alkaloid extracts induce apoptosis in human epidermoid carcinoma cells (A431) through caspase activation and NF-κB inhibition ^{11Reference 11Park SW et al. · 2015In vitroChelidonium majus L. extract induces apoptosis via MAPK-independent NF-κB signalling in human epidermoid carcinoma A431 cells — in vitroView study →}, and in leukaemia lines, where the extract also scavenged DPPH radicals ^{12Reference 12Nadova S et al. · 2008In vitroPotential antioxidant activity, cytotoxic and apoptosis-inducing effects of Chelidonium majus L. extract on leukemia cells — in vitroView study →}.

The individual benzophenanthridines are the presumed cytotoxic agents. The human trial evidence belongs to Ukrain (NSC-631570), a semisynthetic thiophosphoric derivative of celandine alkaloids, not the herb. A phase II pancreatic-cancer trial reported survival gains ^{20Reference 20Gansauge F et al. · 2002RCTNSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer — phase II randomised clinical trialView study →}, but a systematic review found the supporting RCTs to be of poor methodological quality and called for independent replication ^{19Reference 19Ernst E · 2005Systematic reviewUkrain — a new cancer cure? A systematic review of randomised clinical trialsView study →}. The product was never approved.

Gap: the human data belong to Ukrain, a semisynthetic derivative whose trials were of poor quality, not to the plant. Herb-level evidence is purely in vitro, and greater celandine is not a cancer treatment.

Methanol extracts scavenge DPPH radicals, and total phenolic and flavonoid content tracks the measured antioxidant capacity, which peaks at the rosette and early-flowering stages ^{12,17Reference 12Nadova S et al. · 2008In vitroPotential antioxidant activity, cytotoxic and apoptosis-inducing effects of Chelidonium majus L. extract on leukemia cells — in vitroView study →Reference 17Jakovljevic ZD et al. · 2013In vitroSeasonal variability of Chelidonium majus L. secondary metabolites content and antioxidant activity — in vitroView study →}. Most polyphenol-containing plants share this property, and here it sits alongside the alkaloids’ cytotoxicity.

Assay activity only, with no cellular or human endpoint.

Liver injury. Greater celandine is a documented cause of hepatocellular herb-induced liver injury. Causality-assessed case series and reviews describe jaundice, transaminases often exceeding 1,000 IU/L, and a female predominance ^{21,22,23,24Reference 21Teschke R et al. · 2011Case reportHerbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →Reference 22Pantano F et al. · 2017ReviewHepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature — reviewView study →Reference 23Ciornolutchii V et al. · 2024ReviewLiver toxicity caused by Chelidonium majus L.: two cases of herb-induced liver injury and literature reviewView study →Reference 24Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →}. In one German series of 22 reports, symptoms began on average about a month after starting the herb ^{21Reference 21Teschke R et al. · 2011Case reportHerbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports — case seriesView study →}. Patients recovered once it was stopped ^{23,24Reference 23Ciornolutchii V et al. · 2024ReviewLiver toxicity caused by Chelidonium majus L.: two cases of herb-induced liver injury and literature reviewView study →Reference 24Benninger J et al. · 1999Case reportAcute hepatitis induced by greater celandine (Chelidonium majus) — case reportView study →}.

Dose-related. Injury has been reported with capsules, extracts and tea ^{23Reference 23Ciornolutchii V et al. · 2024ReviewLiver toxicity caused by Chelidonium majus L.: two cases of herb-induced liver injury and literature reviewView study →}. The EMA’s herbal committee counted 95 liver cases in the WHO’s international reporting database and judged the benefit–risk balance of oral use negative ^{30Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}.

The committee concluded that the injury appears dose-dependent. In the probable cases where the dose could be worked out, daily alkaloid intake was above 9 mg, and one expert saw no clear link below that level ^{30Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}. Germany limited daily intake of celandine alkaloids to 2.5 mg in 2008 ^{30Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}.

Animal studies. Celandine caused no liver damage in rats fed about 50 and 100 times the usual human dose for four weeks, and it did not worsen acetaminophen liver injury ^{26,27,30Reference 26Mazzanti G et al. · 2009AnimalChelidonium majus is not hepatotoxic in Wistar rats, in a 4-week feeding experiment — animalView study →Reference 27Mazzanti G et al. · 2013Chelidonium majus L. does not potentiate the hepatic effect of acetaminophen — animalView study →Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}. The higher doses did lower the liver’s glutathione and superoxide dismutase, which the EU committee read as a sign of dose-dependent toxicity rather than an idiosyncratic reaction ^{30Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}. Rodent studies have also found the herb protective of the liver ^{6,7Reference 6Biswas SJ et al. · 2008AnimalEfficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice — animalView study →Reference 7Paul A et al. · 2013AnimalPLGA nano-encapsulation of chelidonine enhances its potential against cadmium-induced oxidative stress and hepatic injury in mice — animalView study →}.

Alkaloid cytotoxicity. Isolated alkaloids are directly toxic to liver cells at higher exposures ^{25Reference 25Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}.

Heart rhythm. Whole extracts and the major alkaloids block hERG potassium channels and prolong the cardiac action potential in laboratory models, a theoretical arrhythmia concern at high exposure ^{16Reference 16Orvos 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 →}.

Gallstones and liver disease. Its choleretic action makes it unsuitable in obstructive gallstone or biliary disease. Any pre-existing liver disease is a contraindication.

Interactions. A cardiac-rhythm signal and a risk of added liver toxicity are described from the pharmacology ^{16Reference 16Orvos 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 →}, but no formal human drug-interaction study has been done. Take particular care alongside drugs or other herbs that can injure the liver.