Greater Celandine and Liver Injury

Table of Contents

1. The Plant and Its Yellow Sap
2. The Alkaloids in Greater Celandine
3. Traditional Uses for the Gallbladder, Digestion and Warts
4. The First Case Series from Germany
5. How Strongly the Cases Point to the Herb
6. The Pattern of Injury and the Recovery
7. Cases Reported in Recent Years
8. What Animal and Cell Studies Found
9. Regulatory Actions in Europe
10. Greater Celandine in Combination Digestive Products
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

The Plant and Its Yellow Sap

Greater celandine belongs to the poppy family (Papaveraceae). A 2018 review of its 21 centuries of medicinal use describes it as a common weed of roadsides and waste ground that spreads across all of temperate Europe and Asia and grows well in North America. Like other plants in its poppy subfamily, it produces a yellow-coloured latex in abundance, and the sap leaks freely from any broken stem or leaf. That bright sap is the plant's best-known feature.

The name comes from the Greek chelidon, the swallow. The same review notes that Central and Eastern Europe has used the herb extensively in folk medicine and that, in Slavonic languages especially, it carries many local names. Other names reported in the literature include swallow-wort and, in Chinese, bai-qu-cai.

Greater celandine is a different plant from lesser celandine (pilewort). The two share part of a common name, and the liver-injury research on this page concerns greater celandine.

The Alkaloids in Greater Celandine

The chemistry that interests pharmacologists, and toxicologists, is a group of isoquinoline alkaloids. The 2018 review lists the major pharmacologically relevant ones as berberine, chelerythrine, chelidonine, coptisine and sanguinarine, most of them first isolated more than a century ago.

The European Medicines Agency's Committee on Herbal Medicinal Products (HMPC) gives a fuller list in its 2011 public statement. It reports that the herb contains over 20 different alkaloids, among them alkaloids of the benzylisoquinoline type at 0.01–1%, falling into three groups:

• Benzophenanthridines — chelerythrine, chelidonine, sanguinarine and isochelidonine.
• Protoberberines — berberine, coptisine, dihydrocoptisine and stylopine.
• Protopine.

Berberine is the same yellow alkaloid found in barberry and goldthread and sold on its own as a supplement; it is covered on the site's Berberine page. In greater celandine it is only one alkaloid among many, and the laboratory work described below points more strongly at others in the mix.

The 2018 review adds a point that matters for safety: little is known about how much these alkaloids vary from one wild or cultivated plant to another. A Hanau group's 2012 clinical review similarly describes extracts of the herb as containing more than 20 ingredients, including various biologically active isoquinoline alkaloids.

Traditional Uses for the Gallbladder, Digestion and Warts

The uses described in this section are traditional and folk uses. They are reported here as history, not as findings of clinical trials.

According to the 2018 review, records of greater celandine as a remedy go back as far as the era of Dioscorides, the first-century Greek physician. Partly inspired by the “doctrine of signatures” — the old belief that a plant's appearance shows what it treats, here a yellow sap for yellow jaundice — and partly by folk tradition, healers gave it for jaundice, as a cholagogue (a remedy said to increase the flow of bile), for pain and, quite often, for eye problems.

In more recent European herbal practice, the uses put forward to regulators were narrower. When the HMPC discussed a possible European monograph, two traditional indications were proposed:

• taken by mouth, for symptomatic relief of digestive disorders such as dyspepsia and flatulence;
• applied to the skin, for warts, callus and corns.

The German case series described below notes that greater celandine preparations were frequently prescribed in Germany for gastric and biliary disorders, and a second Erlangen report describes the herb as a well-known remedy frequently used for irritable bowel syndrome. Reviews from 2010 and 2017 also list activities claimed for the herb in herbal medicine — antimicrobial, anti-inflammatory, spasmolytic, anticancer, liver-protective and pain-relieving — together with others, such as cough-relieving, diuretic and “eye-regenerative” effects, that the reviewers note have not been scientifically evaluated.

The 2018 review records that modern pharmacology took an interest in the herb but that it never gained the status of an officially approved, evidence-based herbal medicine. The HMPC concluded in 2011 that evidence of clinical efficacy was lacking for the herb used alone, and that the skin indication was not sufficiently supported by market information on single-herb products.

The First Case Series from Germany

The report that brought greater celandine to the attention of liver specialists came from Erlangen, Germany, in 1999. Benninger and colleagues described 10 cases of acute hepatitis they had seen over two years in people taking greater celandine preparations. Their findings, as stated in the abstract:

• The hepatitis ranged from mild to severe.
• Marked cholestasis — a slowing of bile flow that shows up as jaundice and raised bile-related blood tests — was seen in 5 patients.
• Liver failure did not occur.
• Viral, autoimmune, hereditary, alcohol-related and secondary biliary causes were excluded by laboratory tests and imaging, and liver biopsies were consistent with drug-induced damage.
• After greater celandine was stopped, all patients recovered rapidly, and liver enzymes returned to normal within 2–6 months.
• In 1 patient, taking the herb again by accident led to a second flare of liver inflammation.

In 2003 the same Erlangen group, with Stickel as first author, reported two more patients. All other possible causes of acute liver damage were excluded in both. In one, cholestatic hepatitis returned rapidly after involuntary re-exposure. Both recovered fully after the herb was withdrawn. The authors raised the question of whether the approval of greater celandine products should be re-evaluated, given what they called the lacking evidence for a therapeutic benefit.

A return of liver injury when a person takes the same product again is called a positive re-exposure (or rechallenge). Liver specialists treat it as one of the strongest signs that a product, and not something else, caused the injury. A 2014 analysis of herb-induced liver injury cases with reported re-exposures listed greater celandine among the herbs for which a confirmed positive re-exposure had been documented, alongside kava, germander, green tea and others, with up to 4 such case reports per herb.

How Strongly the Cases Point to the Herb

A single case of liver injury in someone taking an herb does not prove the herb caused it. Doctors use structured scoring systems to grade how likely the link is. The best-known liver-specific system is the scale of the Council for International Organizations of Medical Sciences (CIOMS), which weighs the time to onset, how the liver enzyme alanine aminotransferase (ALT) falls after stopping, risk factors, other medicines and other possible causes. It sorts each case into highly probable, probable, possible, unlikely or excluded.

Rolf Teschke and colleagues at Klinikum Hanau, a teaching hospital in Germany, re-scored the greater celandine cases with this scale in a series of papers.

The 22 German spontaneous reports (2011)

Their 2011 paper took 22 spontaneous reports from Germany. In the original regulatory assessments, which used a method not specific to the liver, causality for greater celandine had been judged probable in 16 cases and possible in 6. Re-scored with the updated CIOMS scale, the results were:

• highly probable — 2 cases;
• probable — 6 cases;
• possible — 10 cases;
• unlikely — 1 case;
• excluded — 3 cases.

So 2 cases were upgraded to highly probable, while 3, 1 and 9 cases were downgraded to excluded, unlikely and possible. The authors concluded that the analysis provides further evidence that greater celandine liver injury exists as a distinct form of herb-induced liver injury, but that, because of poor data quality, the causal link is less strong than had been assumed. They called for liver-specific causality methods and stricter pharmacovigilance.

The 21 published European case reports (2012)

A 2012 paper applied the same scale to 21 published case reports from Europe. Causality was highly probable in 2 and probable in 6; of the remaining 13, causality was possible in 10 and excluded in 3. Alternative diagnoses and poor data quality reduced the scores in some cases. The authors still described “striking evidence” for herb-induced liver injury by greater celandine in the cases with high grades, while noting uncertainty about which ingredient is responsible.

The 16-patient clinical review (2012)

A clinical review from the same group later in 2012 analysed 16 published patients from several European countries in whom causality was probable or highly probable on the CIOMS scale, and described the clinical picture in detail (see the next section).

Other assessments

An Italian report from 2009 described a new case and graded it with the Naranjo scale, a general (not liver-specific) adverse-reaction scale, as a probable relationship. A 2017 literature review from Rome concluded that several cases had been assessed as probably or highly probably connected to the herb with liver-targeted methods and judged the risk-to-benefit ratio of products containing greater celandine to be negative.

The Pattern of Injury and the Recovery

Across the case reviews, the liver injury attributed to greater celandine follows a fairly consistent picture.

• Type of injury. The 2011 and 2012 Hanau papers describe a hepatocellular pattern — damage mainly to the liver cells themselves, with high aminotransferase enzymes — even though the 1999 Erlangen series saw marked cholestasis in half its patients.
• Who was affected. In the 22 German reports, women predominated, and the average age was 56.4 years. A 2024 review of 38 cases found mainly adult women aged 27 to 77.
• Time to onset. In the 22 German reports, the average treatment lasted 36.4 days, and the average time until first symptoms was 29.8 days and until jaundice 35.6 days. The 2024 review found treatment lasting anywhere from 1 week to a year.
• Symptoms. The 2012 clinical review states that jaundice combined with high serum aminotransferases was present in virtually all cases.
• Mechanism. The Hanau group classifies the reaction as idiosyncratic of the metabolic type: it affects only a small, unpredictable minority of users and seems to depend on how an individual's body processes the herb, rather than on an allergic-type immune reaction or on a dose that harms everyone. They found immunologic features lacking.
• Outcome. The 2012 clinical review reports a favourable outcome in its cases despite a severe clinical course. In the Erlangen series, liver enzymes returned to normal within 2–6 months of stopping, and the 2024 review states that stopping the herb generally led to recovery.

Hospitals treat jaundice (yellowing of the skin or eyes), dark urine, pale stools, itching, and nausea with loss of appetite and fatigue as signs of possible liver injury that need prompt assessment. These are the symptoms the case reports below describe.

Cases Reported in Recent Years

Reports have continued since the first wave of German cases, and they now come from outside Germany as well.

• Switzerland, 2022. Doctors in Lausanne described a 32-year-old woman with no previous medical history who came to the emergency department with abdominal pain, jaundice and itching. Blood tests showed acute severe hepatitis with a marked rise in direct bilirubin. After other causes were excluded, she was diagnosed with drug-induced liver injury linked to a combination digestive product containing nine plant extracts, one of them greater celandine. Her symptoms resolved on their own 5 weeks after she stopped the product.
• United States, 2024. A report from North Carolina described acute hepatitis in a 72-year-old man taking a greater celandine supplement for nausea. The authors noted that the earlier case reports came mainly from Europe and that they had found no previous cases from the United States.
• Romania, 2024. Doctors in Cluj-Napoca reported two women. The first, aged 64, came in with jaundice after a month of taking greater celandine capsules for gallstones; she also had stones in the bile duct, and her transaminase levels exceeded 1000 IU/L. She improved after stopping the herb and receiving intravenous therapy, and later had the bile-duct stones removed and her gallbladder taken out. The second, aged 66, had raised liver tests found by chance; she had been drinking greater celandine tea regularly “for health promotion,” and her transaminases returned to normal after treatment.
• Greece, 2026. A report from Athens described a 60-year-old woman with jaundice, yellow eyes, nausea, loss of appetite and fatigue after recently starting an herbal preparation identified as greater celandine. Her aminotransferases, bilirubin and international normalized ratio (INR, a clotting test that reflects liver function) were all abnormally high. Viral hepatitis was excluded, the autoimmune work-up did not support autoimmune hepatitis, and imaging showed no bile-duct blockage. A liver biopsy showed an acute hepatitis-like pattern with portal inflammation, cell death around the central veins, giant-cell change in liver cells and mild fibrosis that did not bridge between areas. After the product was stopped and supportive treatment given, her blood tests improved steadily. The authors note that herb-induced liver injury can be hard to recognise when the herbal product is not mentioned at first.

The 2024 Romanian paper also searched PubMed up to March 2023 and identified 38 cases of herb-induced liver injury associated with greater celandine preparations, reported mostly from Germany. Several forms of the herb were involved, including capsules and tea.

What Animal and Cell Studies Found

One of the puzzles of greater celandine is that the liver injury seen in people has been hard to reproduce in animals.

• In rats, no liver damage. An Italian study gave Wistar rats an extract made from the herbal material behind one human case of liver injury, at doses equivalent to 1.5 and 3 g of herb per kg of body weight per day for 2 or 4 weeks — about 50 and 100 times the doses generally used in humans. Body weight, food intake, liver enzymes and liver tissue under the microscope were unchanged. The extract did produce a slight but significant fall in glutathione and in the antioxidant enzyme superoxide dismutase in the rats' livers, especially at the high dose.
• In rat liver cells, large differences between alkaloids. A German study of individual alkaloids in cultured rat liver cells found the electrically charged alkaloids chelerythrine, coptisine and sanguinarine the most toxic, and the neutral chelidonine, dihydrosanguinarine and protopine less so. The rank order was coptisine > chelerythrine > sanguinarine > chelidonine > protopine > dihydrosanguinarine. The authors note that the herb's extracts and alkaloids had not caused similar effects when given by mouth to pigs or rats, and suggest that liver levels reached in animals were too low to cause harm, probably because some of these alkaloids are very poorly absorbed from the gut.
• In a human liver cell line, the same three alkaloids. A Chinese study exposed HL-7702 liver cells to an extract and measured which alkaloids built up inside the cells. Sanguinarine, coptisine and chelerythrine reached the highest concentrations in the cells and were identified as the main toxic constituents in that cell model.
• Chelidonine forms reactive products. In human liver microsomes (enzyme preparations from liver tissue) and in rats, chelidonine was converted into reactive ortho-quinone products that bound to glutathione. The liver enzymes CYP3A4, CYP1A2, CYP2C19 and CYP2D6 were mainly responsible. The authors present this as a possible explanation for chelidonine's known ability to inhibit these drug-processing enzymes.

None of these studies identifies the cause of the human cases. They show which alkaloids are most toxic to cells in a dish and how one of them is processed, which fits the Hanau group's view of a metabolic, idiosyncratic reaction, but they do not explain why only some people are affected.

Regulatory Actions in Europe

The clearest regulatory statement is the public statement on Chelidonium majus L., herba (reference EMA/HMPC/743927/2010) adopted by the European Medicines Agency's Committee on Herbal Medicinal Products on 13 September 2011, after a public consultation that ended on 15 April 2011. The statement reports:

• In the World Health Organization's Vigisearch database there were 124 reported adverse drug reactions, from 56 spontaneous case reports, affecting the liver and biliary system after intake of medicinal products containing greater celandine, up to 4 May 2011. The large majority came from Germany, with single cases from Austria and Belgium.
• In some European countries, marketing authorisations for medicinal products containing greater celandine had been withdrawn because of concerns about reported adverse effects, particularly liver toxicity. The products withdrawn to that date were those that, according to their product information, would lead to a daily intake of more than 2.5 mg of greater celandine alkaloids.
• The committee considered the evidence supporting a safe oral daily dose limit of not more than 2.5 mg of alkaloids, but stated that it “was not reassured by the scientific rationale or the information available.”
• It concluded that evidence of clinical efficacy was lacking for the herb used on its own, so a “well-established use” indication was not supported.
• It considered the documented traditional uses, but concluded that, given the high number of spontaneously reported liver-biliary reactions and the withdrawals in member states, the benefit-risk assessment of oral use is negative with respect to establishing a European monograph.
• It stated that safer herbal medicinal products are available for the indication in question.
• For use on the skin, it considered the indication not sufficiently supported by market information on single-herb products.
• It left the door open: if new information on the clinical safety and efficacy of the herb as a single ingredient for oral use became available, the committee may re-assess it.

As a result, no European Union herbal monograph exists for greater celandine. The public statement refers readers to a separate HMPC assessment report for the detailed toxicological review; that longer report is not summarised on this page.

The 2.5 mg daily alkaloid limit also appears in the scientific literature: the 2019 German cell study cites a safe oral daily dose limit of not more than 2.5 mg of alkaloids established in the European Union, based on the reported cases.

Greater Celandine in Combination Digestive Products

Greater celandine is not only sold on its own. It has also been one ingredient in multi-herb liquid preparations for functional digestive complaints such as indigestion and irritable bowel symptoms. The 2022 Swiss case report describes one such product as a formulation of 9 medicinal plant extracts, including greater celandine, and as one of the most used herbal preparations in Europe. That case is the one summarised above: acute severe hepatitis in a young woman, resolving 5 weeks after the product was stopped. The report's authors describe the product as generally safe and well tolerated in controlled studies, with occasional documented cases of drug-induced liver injury.

Several points apply to combination products in the sources read for this page:

• In a combination, greater celandine is one extract among several, so the amount of its alkaloids per daily dose depends on the formulation. The withdrawals described in the HMPC statement concerned products that would give more than 2.5 mg of alkaloids a day.
• When a person taking a multi-herb product develops liver injury, the case report usually cannot say which ingredient was responsible.
• The HMPC public statement addresses the herb itself and single-ingredient use; it does not set out a separate conclusion for combination products.
• The Swiss, US and Greek reports all stress that herbal products are often left out of the medication history. Each of these patients was diagnosed only after the herbal product came to light.

The site's Angelica digestive and bitter tonic page discusses the research on such combinations for indigestion.

What Is Not Known

• Which ingredient is responsible. Both the 2012 Hanau papers state that there is uncertainty about the culprit compound or compounds. Cell studies point to sanguinarine, coptisine and chelerythrine, but cells in a dish are not people.
• Why only some people are affected. The reaction is described as idiosyncratic, and no test exists to predict who will react. The 2024 Romanian paper notes there is no definitive laboratory test to identify the causative agent.
• How common the injury is. The case counts — 10 in the first series, 22 German spontaneous reports, 56 case reports in the WHO database up to 2011, 38 published cases by 2023 — are counts of reports, not rates. The number of people who took the herb without harm is not known.
• Whether there is a safe dose. The HMPC was not reassured by the evidence for a 2.5 mg daily alkaloid limit.
• How products vary. The 2018 review notes that little is known about natural variation in the plant's alkaloids, and the case reports involve capsules, teas, extracts and combinations of differing make-up.
• Why animals do not show the injury. Rats given very high doses showed no liver damage, and a 2019 study suggests poor absorption of some alkaloids may explain the gap.
• Whether it works. The HMPC found evidence of clinical efficacy lacking for the herb alone, and the 2018 review describes recent reports of anticancer effects as controversial and sometimes insufficiently proven.

Questions about any herbal product, especially in someone with liver disease or taking other medicines, are for a clinician.

Key Research Papers

1. Benninger J, Schneider HT, Schuppan D, Kirchner T, Hahn EG. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterology. 1999;117(5):1234-7. PubMed PMID: 10535888
2. Stickel F, Pöschl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D. Acute hepatitis induced by Greater Celandine (Chelidonium majus). Scand J Gastroenterol. 2003;38(5):565-8. PubMed PMID: 12795472
3. Teschke R, Glass X, Schulze J. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports. Regul Toxicol Pharmacol. 2011;61(3):282-91. PubMed PMID: 21893153
4. Teschke R, Glass X, Schulze J, Eickhoff A. Suspected Greater Celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe. Eur J Gastroenterol Hepatol. 2012;24(3):270-80. PubMed PMID: 22189691
5. Teschke R, Frenzel C, Glass X, Schulze J, Eickhoff A. Greater Celandine hepatotoxicity: a clinical review. Ann Hepatol. 2012;11(6):838-48. PubMed PMID: 23109446
6. Teschke R, Genthner A, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: analysis of cases with initially reported positive re-exposure tests. Dig Liver Dis. 2014;46(3):264-9. PubMed PMID: 24315480
7. Moro PA, Cassetti F, Giugliano G, Falce MT, Mazzanti G, Menniti-Ippolito F, Raschetti R, Santuccio C. Hepatitis from Greater celandine (Chelidonium majus L.): review of literature and report of a new case. J Ethnopharmacol. 2009;124(2):328-32. PubMed PMID: 19397968
8. Pantano F, Mannocchi G, Marinelli E, Gentili S, Graziano S, Busardò FP, di Luca NM. Hepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature. Eur Rev Med Pharmacol Sci. 2017;21(1 Suppl):46-52. PubMed PMID: 28379595
9. Zielińska S, Jezierska-Domaradzka A, Wójciak-Kosior M, Sowa I, Junka A, Matkowski AM. Greater Celandine's Ups and Downs-21 Centuries of Medicinal Uses of Chelidonium majus From the Viewpoint of Today's Pharmacology. Front Pharmacol. 2018;9:299. PubMed PMID: 29713277
10. Leroy A, Perrin H, Porret R, Sempoux C, Chtioui H, Fraga M, Bart PA. Iberogast®-Induced Acute Liver Injury-A Case Report. Gastro Hep Adv. 2022;1(4):601-603. PubMed PMID: 39132058
11. Power S, Barritt AS 4th. A Yellow Flower With Jaundice Power: Liver Injury Attributed to Greater Celandine. ACG Case Rep J. 2024;11(5):e01347. PubMed PMID: 38682076
12. Ciornolutchii V, Ismaiel A, Sabo CM, Al Hajjar N, Seicean A, Dumitrascu DL. A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L.: Report of Two Cases of Herb-Induced Liver Injury and Literature Review. Am J Ther. 2024;31(4):e382-e387. PubMed PMID: 38820341
13. Adamidis N, Adamidi S, Georgakopoulou VE, Miliou S, Karampela A, Stratopoulos E, Margariti T, Sakizlis G, Adamidis S. Chelidonium majus-Induced Hepatitis: A Case Report of Herb-Induced Liver Injury. Cureus. 2026;18(5):e109572. PubMed PMID: 42359199
14. Mazzanti G, Di Sotto A, Franchitto A, Mammola CL, Mariani P, Mastrangelo S, Menniti-Ippolito F, Vitalone A. Chelidonium majus is not hepatotoxic in Wistar rats, in a 4 weeks feeding experiment. J Ethnopharmacol. 2009;126(3):518-24. PubMed PMID: 19761826
15. Gao L, Schmitz HJ, Merz KH, Schrenk D. Characterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes. Toxicol Lett. 2019;311:91-97. PubMed PMID: 31054355
16. Wu C, Wang X, Xu M, Liu Y, Di X. Intracellular Accumulation as an Indicator of Cytotoxicity to Screen Hepatotoxic Components of Chelidonium majus L. by LC-MS/MS. Molecules. 2019;24(13):2410. PubMed PMID: 31261913
17. Liu Y, Peng Y, Zhang Z, Guo X, Ji M, Zheng J. In vitro and in vivo studies of the metabolic activation of chelidonine. Chem Biol Interact. 2019;308:155-163. PubMed PMID: 31102647

PubMed Topic Searches

1. Chelidonium majus hepatotoxicity
2. Greater celandine liver injury
3. Chelidonium alkaloids and toxicity
4. Herb-induced liver injury causality assessment

Connections

• Heart, Liver and Metabolic Herbs — the category this herb belongs to
• Angelica: Digestive and Bitter Tonic — combination digestive products that include greater celandine
• Liver Injury from Supplements — herb and supplement liver injury across many products
• Skullcap: Germander Adulteration and Liver Safety — another herb with confirmed re-exposure cases
• He Shou Wu Liver Health and Hepatotoxicity Warning — an idiosyncratic herbal liver injury from Asia
• Kava — the other European herbal liver-injury story of the same years
• Berberine — one of the greater celandine alkaloids, studied on its own
• Milk Thistle — the most studied liver herb in the same category

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