Greater Celandine

The botanical name of this herb, Chelidonium, stems from the Greek word chelidon, which refers to a swallow (the bird), was actually given to the herb by the famous herbalist Pliny, because it comes into flower when the swallows appear in spring, and fades when they leave again. He suggested the traditional use of using the herbs juice to remove films from the cornea of the eye was first discovered by the swallows, further leading to a connection between these 2 organisms ^{31,32Reference 31Bone K · 2013Principles and Practice of PhytotherapyReference 32Grieve M · 1931A Modern Herbal — Celandine, GreaterView study →}.

Both the root and the aerial parts of this flower have been used medicinally and contain similar alkaloids; the aerial parts are much preferred and used more commonly medicinally ^{31Reference 31Bone K · 2013Principles and Practice of Phytotherapy}.

Traditional uses of chelidonium include: Gallbladder disease and stones, liver disease such as jaundice, to aid detoxification via liver and bowel, gastric ulcers, migraines, and skin conditions such as warts, ringworm, and fungal infection ^{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 China, chelidonium was used for similar indications as it was used in Europe such as gastritis, gastric ulcers, enteritis, jaundice, and abdominal pain. They also used it here however to treat bronchitis, and whooping cough ^{31Reference 31Bone K · 2013Principles and Practice of Phytotherapy}.

Actions

Clears heat, cools, drying ^{29Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}.

Indications

Abdominal pain, peptic ulcers, chronic bronchitis, whooping cough ^{33Reference 33Bone K · 2003A Clinical Guide to Blending Liquid Herbs}. Great for conditions involving damp-heat (such as congested bile) ^{29Reference 29Gilca M et al. · 2010ReviewChelidonium majus — an integrative review: traditional knowledge versus modern findings — reviewView study →}. It’s mainly used to treat blood stasis due to stagnation of Qi, relieve pain, promote diuresis in edema conditions (also seen as stagnation), relieve cough and treat jaundice.

The bitter taste of Chelidonium majus is 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 any controlled human data. A placebo-controlled, double-blind multicentre study (n=76, 3 weeks) of Cholagogum F Nattermann — dried extracts of Chelidonium and Curcuma — reported faster relief of dull and colicky right-upper-quadrant pain from biliary dyskinesia than placebo, with no side effects, though 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. Mechanistically, a whole-herb extract increased bile flow in the isolated perfused rat liver, supporting a genuine choleretic action ^{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: no placebo-controlled trial of celandine alone; the one positive human result is confounded by turmeric, and choleretic stimulation is precisely the action that is unwise in obstructive gallstone disease.

A methanol extract suppressed collagen-induced arthritis in mice, lowering TNF-α, IL-6 and IFN-γ, reducing B- and γδ-T-cell populations and raising 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 →} — a coherent immunomodulatory picture that fits the traditional “heat-clearing” framing. 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 →}, and 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 →}. The mechanism is therefore mapped across enzyme, cell and whole-animal levels.

Gap: entirely preclinical; no human inflammatory endpoint has been tested, and the most active anti-inflammatory alkaloids overlap with the ones implicated in cytotoxicity.

Rodent work is surprisingly consistent: 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 →}, and chelidonine — especially as a PLGA nanoformulation — protected mouse liver against cadmium-induced oxidative injury, restoring GSH and normalising ALT/AST/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 →}. The signal is real but preclinical, and it collides with the clinical record.

Gap: the paradox is the story — the same herb repeatedly protects rodent livers yet is a documented cause of idiosyncratic human liver injury ^{21,22,23Reference 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 →}. Isolated alkaloids are directly cytotoxic to rat hepatocytes at higher exposures ^{25Reference 25Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}, so “hepatoprotective” cannot be read as “liver-safe.”

Across independent screens the alkaloid fraction shows activity against gram-positive bacteria — Staphylococcus aureus including MRSA, streptococci — and against biofilms, 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 tobamovirus 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 →}, consistent with the traditional topical use of the alkaloid-dense latex on warts and skin infections.

Gap: all in vitro; activity tracks alkaloid content and extract type, and no controlled human infection study — topical or systemic — has been done.

The traditional analgesic reputation has a plausible neuropharmacological basis but no human trials. 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 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 central to pain transmission. Whole extracts and major alkaloids also block hERG potassium channels and alter cardiac action potentials, a finding framed as a cardiac-safety concern rather than a therapeutic mechanism ^{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, suggesting a possible role in opioid tapering ^{15Reference 15Yoo JH et al. · 2006AnimalInhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice — animalView study →}.

Gap: all animal or ex vivo; the same ion-channel promiscuity that could explain analgesia (hERG block) is a safety liability, and no clinical analgesia data exist.

Cell-line data are broad and repeatable: whole-herb and alkaloid extracts induce apoptosis in human epidermoid carcinoma (A431) via 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, with the extract also scavenging 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 drivers. The human trial evidence, however, 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 urged independent replication ^{19Reference 19Ernst E · 2005Systematic reviewUkrain — a new cancer cure? A systematic review of randomised clinical trialsView study →}, and the product was never approved.

Gap: the strongest-sounding “human” data don’t apply to the herb as used; herb-level evidence is purely in vitro, and celandine is not a cancer therapy.

Methanol extracts scavenge DPPH radicals and total phenolic/flavonoid content correlates with 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 →}. This is a genuine but generic chemical property shared by most polyphenol-containing plants, and here it is entangled with the alkaloids’ cytotoxicity rather than being a clean protective effect.

Gap: in vitro assay activity only; no cellular or human antioxidant endpoint, and antioxidant framing understates the toxicological weight of the same extracts.

Greater celandine is a documented cause of idiosyncratic, hepatocellular herb-induced liver injury: causality-assessed case series and reviews describe jaundice and transaminases often exceeding 1000 IU/L, with a female predominance, latency of roughly 4–8 weeks, and recovery on stopping the herb ^{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 →}. The risk is not dose-predictable — it has been reported with capsules, extracts and even tea at ordinary intakes ^{23Reference 23Ciornolutchii V et al. · 2024ReviewLiver toxicity caused by Chelidonium majus L.: two cases of herb-induced liver injury and literature reviewView study →} — which is why the EMA/HMPC declined a traditional-use registration and why the herb is best avoided internally ^{30Reference 30European Medicines Agency · 2011Assessment report on Chelidonium majus L., herbaView study →}. Notably, celandine showed no hepatotoxicity in rat feeding and acetaminophen-potentiation studies ^{26,27Reference 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 →}, which is exactly why the human injury is read as idiosyncratic rather than straightforward dose toxicity — the animal safety data do not reassure here. This clinical picture is also paradoxical against consistent rodent hepatoprotective results ^{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 →}; 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 →}, so “hepatoprotective” preclinical findings must not be read as liver-safe. Whole extracts and major alkaloids also block hERG potassium channels and alter cardiac action potentials in in-vitro/animal 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 →}. Its choleretic action makes it unsuitable in obstructive gallstone or biliary disease, and any pre-existing liver disease is a contraindication given the injury risk — not merely a caution.

Interactions — scope note. A hERG/cardiac-safety signal and an additive-hepatotoxicity concern are described mechanistically ^{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 (e.g. clinical CYP450) study was identified in this package. Treat concurrent hepatotoxic drugs and other herb-induced-liver-injury-associated botanicals as a caution, not a proven interaction — absence of interaction studies is not evidence of safety.