Celandine

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Research Overview

Across the abstracts, research on greater celandine (Chelidonium majus) clusters into three main areas: (1) safety—especially herb-induced liver injury (HILI) and hepatotoxicity; (2) phytochemistry and in vitro bioactivity, including antioxidant capacity, enzyme inhibition (e.g., cholinesterase and tyrosinase), and cytotoxicity against cancer cell lines; and (3) formulation/engineering approaches (e.g., essential oils encapsulated in chitosan nanoparticles) aimed at enhancing delivery and testing anticancer effects in cell models. A smaller clinical/dermatologic theme concerns traditional topical use of the plant’s milky sap for viral warts, largely discussed via literature review and case-based observations rather than controlled trials.

The strongest evidence in this set supports a clinically relevant safety signal: greater celandine is repeatedly listed among herbs with probable/highly probable causality for hepatotoxicity in compilations of case reports and regulatory-style assessments, with presentations ranging from mild hepatitis to acute liver failure. At the same time, the evidence base is complicated by diagnostic uncertainty: nearly half of initially suspected HILI cases in broader analyses had alternative explanations (e.g., viral hepatitis, autoimmune disease, alcohol-related liver disease, comedication-related DILI), underscoring that attribution requires rigorous causality assessment and exclusion of competing diagnoses. For efficacy, the most consistent findings are preclinical—extracts (notably methanolic) show high levels of phenolics/alkaloids with strong antioxidant and enzyme-inhibitory activity, and both extracts and essential-oil nanoparticle formulations demonstrate dose-dependent cytotoxicity in cancer cell lines—yet these results remain laboratory-based and do not establish clinical benefit.

Key gaps include: (1) better epidemiology and risk characterization for celandine-associated hepatotoxicity (incidence, dose–response, product composition/contaminants, host susceptibility, and outcomes), using standardized, liver-specific causality methods and careful evaluation of alternative causes; (2) clinical efficacy studies for proposed indications (e.g., dermatologic wart treatment and any anticancer claims), moving from case reports and in vitro assays to well-designed controlled trials with defined preparations; and (3) mechanistic work linking specific constituents (e.g., isoquinoline alkaloids and essential-oil components) to both therapeutic targets and liver injury pathways, alongside pharmacokinetics, herb–drug interaction studies, and quality-control standardization to improve reproducibility and safety assessment.

1. What conditions has Celandine been studied for?

  • Herb-induced liver injury (HILI) / hepatotoxicity: Greater celandine (Chelidonium majus) is repeatedly discussed in reviews and compilations of herbal hepatotoxicity, including cases assessed as “probable” or “highly probable” using liver-specific causality methods.

  • Cancer (antitumor/cytotoxic effects):

    • In vitro cytotoxicity against multiple cancer cell lines (e.g., pancreatic PANC-1, colon HT-29, breast MDA-MB-231; murine PANC02).

    • Preliminary in vivo testing in a metastatic murine pancreatic cancer model (metastasis counts and primary tumor weight assessed).

    • Nanoparticle/essential-oil formulations tested in vitro on MCF-7 breast cancer cells (dose-dependent effects reported).

    • Extract comparisons (methanol/ethyl acetate/water) assessed for cytotoxicity against gastric (HGC-27) and colon (HT-29) cancer cells, with comparison to a non-cancer line (HEK293).

  • Viral warts (cutaneous warts; papillomavirus-related): A literature analysis plus a case report describes folk use of the milky sap/latex applied topically for viral warts.

  • Enzyme inhibition relevant to neurologic/dermatologic targets (preclinical): Extracts were tested for inhibition of cholinesterase and tyrosinase activity (enzyme inhibitory assays).

  • Antioxidant activity (preclinical): Extracts assessed for antioxidant capacity, linked to phenolic/alkaloid content.

  • Potential digestive-system relevance via kynurenic acid (KYNA) content: Greater celandine was identified as one of several herbs containing KYNA; authors suggest KYNA may have therapeutic potential “especially in the digestive system,” but this is not a direct clinical trial of celandine for a digestive condition.

2. Does it work in treating those conditions? Summarize the evidence.

  • Cancer: Evidence is mainly preclinical (cell culture and limited animal data).

    • In vitro: An 80% ethanolic extract (and a defatted version) showed cytotoxicity against PANC-1 and HT-29 with IC50 values around ~20.6–20.7 µg/mL, and more moderate activity against MDA-MB-231 (IC50 ~73.9 µg/mL). Activity was also reported against murine PANC02 (IC50 ~34–36 µg/mL). Low to almost no cytotoxicity was reported on certain primary endometrium cancer cells and on normal fibroblasts (3T3) for the defatted extract in that study.

    • In vivo (mouse metastatic pancreatic model): Treatment with 1.2 mg/kg defatted extract was associated with significantly fewer metastases versus control, but did not reduce primary tumor weight. This was described as a preliminary study.

    • Formulation studies (nanoparticles/essential oils): Chitosan nanoparticles loaded with greater celandine essential oils showed dose-dependent effects on MCF-7 cells in an MTT assay, but the abstract fragment does not provide complete potency metrics or clinical relevance.

    • Bottom line: These findings suggest biological activity, but they do not establish clinical effectiveness for cancer treatment in humans.

  • Viral warts: Evidence in the provided abstracts is very limited—a literature review plus a single pediatric case description of topical milky sap use. This is insufficient to conclude efficacy, especially without controlled trials, standardized preparations, and safety monitoring.

  • Antioxidant and enzyme inhibition (cholinesterase, tyrosinase): Extracts—particularly methanol extracts—showed strong antioxidant activity and strong inhibitory activity in enzyme assays. These are mechanistic/preclinical results and do not demonstrate clinical benefit for Alzheimer’s disease, hyperpigmentation, or other conditions.

  • Hepatoprotection claims: One review notes celandine has been claimed to be hepatoprotective, but also concludes that reported hepatotoxicity cases (assessed with liver-targeted causality methods) and the absence of considerable proven benefits make the overall risk–benefit ratio negative.

3. What health benefits does it have?

  • Potential antitumor activity (preclinical): Extracts containing benzylisoquinoline alkaloids (identified in one study as chelidonine, sanguinarine, chelerythrine, protopine) demonstrated cytotoxicity against several cancer cell lines, and a defatted extract reduced metastasis counts in a mouse model (without shrinking primary tumors).

  • Antioxidant activity (preclinical): Extracts—especially methanol extracts with higher phenolic/alkaloid content—showed very strong antioxidant activity in laboratory assays.

  • Enzyme inhibitory activity (preclinical): Methanol extracts showed strong inhibition of cholinesterase and tyrosinase in vitro, suggesting possible relevance to neurochemical and pigmentation-related pathways, though clinical benefit is unproven.

  • Possible topical benefit for warts (low-quality evidence): Folk use and anecdotal reports (including a described pediatric case) suggest some people perceive benefit from topical latex for viral warts, but this remains unconfirmed by robust clinical trials.

  • Contains kynurenic acid (KYNA): Greater celandine was among herbs found to contain KYNA; authors propose KYNA may have therapeutic potential (notably for the digestive system), but this is indirect evidence and not proof of benefit from celandine supplementation.

4. Does it have any downsides or side effects?

  • Liver injury risk (key concern): Multiple hepatotoxicity reviews list greater celandine among herbs associated with hepatotoxicity ranging from mild hepatitis to acute liver failure. A dedicated review of Chelidonium majus concludes hepatotoxicity cases have been reported as probable/highly probable after liver-targeted causality assessment and characterizes the injury as a distinct HILI, likely idiosyncratic (metabolic type).

  • Risk–benefit concerns: The same review explicitly states that, given hepatotoxicity evidence and the absence of considerable proven benefits, the risk–benefit ratio can be considered negative for products containing greater celandine.

  • Diagnostic uncertainty in suspected HILI: A review of suspected herb-induced liver injury cases found alternative causes in 48.5% of 573 cases (e.g., viral hepatitis, autoimmune disease, alcohol-related disease, comedication-related DILI/HILI). This does not negate celandine risk, but it highlights that attributing liver injury to an herb can be complex and requires careful evaluation.

  • General limitations and unknowns: Incidence rates of herbal hepatotoxicity are described as largely unknown, and standard DILI causality tools are noted as not validated for herbal products in one review—meaning true risk magnitude and predictors remain uncertain.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

The provided abstracts do not report specific pharmacogenomic findings for greater celandine (e.g., gene variants that predict benefit, toxicity, or altered metabolism).

  • What can be inferred (with limitations): The hepatotoxicity review characterizes celandine-associated liver injury as idiosyncratic and of a metabolic type. Idiosyncratic metabolic reactions can sometimes be influenced by genetic variation in drug-metabolizing enzymes or immune pathways, but no specific genes or variants are identified in these abstracts.

  • Practical implication: Because no validated genetic markers are provided here, pharmacogenomic testing cannot currently be used (based on these abstracts) to identify who will benefit or who is at higher risk of celandine-related adverse effects.

References

  1. Review article: herbal and dietary supplement hepatotoxicity.
    C Bunchorntavakul, K R Reddy (2013) - Alimentary pharmacology & therapeutics
  2. Synthesis and characterization of chitosan nanoparticles loaded with greater celandine (Chelidonium majus L.) essential oil as an anticancer agent on MCF-7 cell line.
    Sadra Hesami, Shahabeddin Safi, Kambiz Larijani, Hassanali Naghdi Badi, Vahid Abdossi, Milad Hadidi (2022) - International journal of biological macromolecules
  3. Romanian Wild-Growing
    Adina-Elena Segneanu, Gabriela Vlase, Titus Vlase, Maria-Viorica Ciocalteu, Cornelia Bejenaru, Gabriela Buema, Ludovic Everard Bejenaru, Eugen Radu Boia, Andrei Dumitru, Simina Boia (2024) - Plants (Basel, Switzerland)
  4. Herbal hepatotoxicity: a tabular compilation of reported cases.
    Rolf Teschke, Albrecht Wolff, Christian Frenzel, Johannes Schulze, Axel Eickhoff (2012) - Liver international : official journal of the International Association for the Study of the Liver
  5. Chemical characterization of three different extracts obtained from Chelidonium majus L. (Greater celandine) with insights into their in vitro, in silico and network pharmacological properties.
    Milena Terzic, Shaimaa Fayez, Nouran M Fahmy, Omayma A Eldahshan, Abdullahi Ibrahim Uba, Sathish Kumar M Ponniya, Selami Selvi, Nilofar, Ismail Koyuncu, Özgür Yüksekdağ, Gokhan Zengin (2024) - Fitoterapia
  6. Enhancing Wound Healing: A Comprehensive Review of Sericin and
    Ana Borges, María Luisa Martín Calvo, Josiana A Vaz, Ricardo C Calhelha (2024) - Materials (Basel, Switzerland)
  7. Bioassay-Guided Assessment of Antioxidative, Anti-Inflammatory and Antimicrobial Activities of Extracts from Medicinal Plants via High-Performance Thin-Layer Chromatography.
    Marko D Jović, Snezana Agatonovic-Kustrin, Petar M Ristivojević, Jelena Đ Trifković, David W Morton (2023) - Molecules (Basel, Switzerland)
  8. Herbal hepatotoxicity: suspected cases assessed for alternative causes.
    Rolf Teschke, Johannes Schulze, Alexander Schwarzenboeck, Axel Eickhoff, Christian Frenzel (2013) - European journal of gastroenterology & hepatology
  9. Modulatory Effect of
    Sylwia Zielińska, Monika Ewa Czerwińska, Magdalena Dziągwa-Becker, Andrzej Dryś, Mariusz Kucharski, Anna Jezierska-Domaradzka, Bartosz J Płachno, Adam Matkowski (2020) - Molecules (Basel, Switzerland)
  10. Milky Sap of Greater Celandine (
    Joanna Nawrot, Małgorzata Wilk-Jędrusik, Sylwia Nawrot, Krzysztof Nawrot, Barbara Wilk, Renata Dawid-Pać, Maria Urbańska, Iwona Micek, Gerard Nowak, Justyna Gornowicz-Porowska (2020) - International journal of environmental research and public health
  11. Distribution, synthesis, and absorption of kynurenic acid in plants.
    Michal P Turski, Monika Turska, Wojciech Zgrajka, Magdalena Bartnik, Tomasz Kocki, Waldemar A Turski (2011) - Planta medica
  12. Hepatotoxicity induced by greater celandine (Chelidonium majus L.): a review of the literature.
    F Pantano, G Mannocchi, E Marinelli, S Gentili, S Graziano, F P Busardò, N M di Luca (2017) - European review for medical and pharmacological sciences
  13. In vitro and in vivo investigations on the antitumour activity of Chelidonium majus.
    Rica Capistrano I, An Wouters, Filip Lardon, Claudia Gravekamp, Sandra Apers, Luc Pieters (2015) - Phytomedicine : international journal of phytotherapy and phytopharmacology
  14. The Activity of
    Oskar Musidlak, Alicja Warowicka, Justyna Broniarczyk, Damian Adamczyk, Anna Goździcka-Józefiak, Robert Nawrot (2022) - International journal of molecular sciences
  15. Effects of Abiotic Elicitors on Expression and Accumulation of Three Candidate Benzophenanthridine Alkaloids in Cultured Greater Celandine Cells.
    Seyed Mohammad Hashemi, Mohammad Reza Naghavi, Esmaeil Bakhshandeh, Mehdi Ghorbani, Chanditha Priyanatha, Peiman Zandi (2021) - Molecules (Basel, Switzerland)
  16. Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential - a safety approach.
    Péter Orvos, László Virág, László Tálosi, Zsuzsanna Hajdú, Dezső Csupor, Nikoletta Jedlinszki, Tamás Szél, András Varró, Judit Hohmann (2015) - Fitoterapia
  17. The Synergistic Mechanism of
    Peng Chen, Xin-Ye Ji, Jian-Ting Feng, Xiao-Qin Wang, Bo Zhang (2024) - Molecules (Basel, Switzerland)
  18. Screening of Chelidonium majus isoquinoline alkaloids reveals berberine and chelidonine as selective ligands for the nuclear receptors RORβ and HNF4α, respectively.
    Sohrab Salehi, Espen Schallmayer, Nils Bandomir, Annette Kärcher, Jan-Frederik Güth, Pascal Heitel (2024) - Archiv der Pharmazie
  19. Investigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques.
    Wioleta Jesionek, Emilia Fornal, Barbara Majer-Dziedzic, Ágnes M Móricz, Wassil Nowicky, Irena M Choma (2016) - Journal of chromatography. A
  20. Effect of chelidonine on growth, invasion, angiogenesis and gene expression in head and neck cancer cell lines.
    Ruth Herrmann, Jeanette Roller, Christine Polednik, Marianne Schmidt (2018) - Oncology letters


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