# Chelerythrine (Chelidonium majus / Macleaya cordata alkaloid)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/chelerythrine-chelidonium-majus-macleaya-cordata-alkaloid
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-04
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Chelidonium majus alkaloid, Chelerythrine chloride, Benzophenanthridine alkaloid, C21H18NO4, Macleaya cordata alkaloid

## Overview

Chelerythrine (C21H18NO4) is a benzophenanthridine alkaloid that exerts broad biological activity primarily by inhibiting protein kinase C (PKC) with an IC50 of 660 nM, disrupting Bcl-xL/Bak apoptotic signaling, intercalating DNA, and damaging bacterial cell membranes. Preclinical data demonstrate in vitro cytotoxicity against multiple cancer cell lines at 2.5–20 µM, antibacterial activity against Group B Streptococcus at MIC/MBC of 256/512 µg/mL, and a rapid pharmacokinetic profile in pigs (Cmax <2 h oral; T1/2 ≈ 2.03 h), though no human clinical trials have been completed.

## Health Benefits

- **Anticancer (Apoptosis Induction)**: Chelerythrine disrupts the BclXL–Bak interaction (IC50 ≈ 1.5 µM), displacing Bax and triggering the intrinsic apoptotic cascade; in vitro cytotoxicity has been demonstrated against HeLa, A549, and other cell lines at concentrations of 2.5–20 µM.
- **Protein Kinase C Inhibition**: As a potent, cell-permeable PKC inhibitor (IC50 = 660 nM), chelerythrine suppresses downstream proliferative and survival signaling; it acts competitively with the phosphate acceptor substrate and non-competitively with ATP, providing mechanistic selectivity.
- **Antibacterial Activity**: Purified chelerythrine chloride produces inhibition zones of 10.76–14.32 mm against Group B Streptococcus (GBS) at 0.5–2 mg/mL, causing membrane collapse, cellular shrinkage, fluid leakage, and efflux of ATP, AKP, Na+, K+, Ca2+, and Mg2+ ions, with bactericidal action at 2–8× MIC within 24 hours.
- **DNA Intercalation and G-Quadruplex Stabilization**: The iminium form of chelerythrine (dominant at pH 1–6) intercalates DNA and selectively stabilizes G-quadruplex (G4) structures over duplex DNA via hydrogen bonding of its benzo-1,3-dioxolo group to guanine bases, a mechanism of potential relevance to telomerase inhibition and oncogene suppression.
- **[Anti-inflammatory](/ingredients/condition/inflammation) Activity**: Chelerythrine modulates MAPK signaling pathways independently of PKC inhibition and antagonizes G-protein-coupled CB1 cannabinoid receptors, contributing to attenuation of inflammatory cascades in preclinical cell-based models.
- **Antiplatelet Effects**: Preclinical evidence indicates chelerythrine interferes with platelet activation pathways, likely through PKC-dependent mechanisms that regulate integrin signaling and thromboxane release, though specific quantitative platelet aggregation data from isolated chelerythrine studies remain limited.
- **[Antiviral](/ingredients/condition/immune-support) Potential**: Chelerythrine has demonstrated broad antiviral activity in cell-based assays, attributed to its nucleic acid-binding capacity and membrane-disrupting properties; precise EC50 values and specific viral targets require further mechanistic characterization in controlled studies.

## Mechanism of Action

Chelerythrine competitively inhibits protein kinase C (PKC) at the phosphate acceptor binding site (IC50 = 660 nM) and non-competitively inhibits it at the ATP site, suppressing downstream pro-survival and proliferative MAPK signaling independently of PKC activity. At the [mitochondrial](/ingredients/condition/energy) apoptotic level, it displaces Bax from BclXL and disrupts BclXL–Bak protein–protein interactions (IC50 ≈ 1.5 µM), committing cells to caspase-dependent apoptosis. The pH-sensitive iminium form of the molecule intercalates into DNA and selectively stabilizes G-quadruplex structures through hydrogen bonding via its benzo-1,3-dioxolo moiety, while the quaternary nitrogen carbon is susceptible to nucleophilic attack—a feature linked to both bioactivity and inherent cytotoxicity. Antibacterially, chelerythrine destabilizes bacterial cell walls and plasma membranes, causing structural collapse, ion dysregulation (efflux of Na+, K+, Ca2+, Mg2+), and ATP leakage, resulting in bactericidal effects at concentrations 2–8× MIC.

## Clinical Summary

No human clinical trials evaluating chelerythrine as an isolated compound have been identified in the published literature. Safety and pharmacokinetic parameters have been characterized in animal models, with pig studies demonstrating rapid absorption, short half-life (~2.03 h), and acceptable tolerability at 5 mg/kg/day without genotoxic or hepatotoxic signals. In vitro cytotoxicity data against both cancer (HeLa, A549) and normal (HL-7702 hepatocyte) cell lines at 2.5–20 µM raise concerns about a narrow therapeutic window that must be resolved in dose-escalation studies before clinical application. Confidence in any clinical benefit claim is therefore low; chelerythrine remains an investigational compound with promising preclinical mechanistic data but requiring Phase I human trials to define safety, pharmacokinetics, and preliminary efficacy.

## Nutritional Profile

Chelerythrine is not a macronutrient or micronutrient and contributes no caloric, protein, fat, carbohydrate, vitamin, or mineral value in any nutritional sense. It is a secondary metabolite alkaloid (C21H18NO4, MW 383.83 as free base; 383.83 as chloride salt when accounting for the HCl form) present in plant tissues at concentrations that vary by species, plant part, and growth conditions but are not standardized in food-grade contexts. Its bioavailability is influenced strongly by pH: the iminium (cationic) form predominates at physiological gastric pH (1–6) and binds efficiently to nucleic acids and proteins, while the alkanolamine pseudo-base form predominates at alkaline pH (8.5–11) and preferentially associates with serum albumin, affecting distribution and free fraction in plasma. Rapid first-pass [metabolism](/ingredients/condition/weight-management) to dihydrochelerythrine in mammalian systems further modifies the effective bioavailable fraction of the parent compound.

## Dosage & Preparation

- **Purified Chloride Salt (Research Grade)**: Chelerythrine chloride (≥98% purity, MW 383.83) is the standard form used in laboratory and preclinical research; it is soluble in water and DMSO at up to 3.84 mg/mL (10 mM) and stored desiccated at −20°C.
- **Stock Solutions**: Prepared at 0.1–5 mM in water or DMSO for in vitro experiments; DMSO concentration in cell assays is kept ≤0.1% to avoid solvent cytotoxicity artifacts.
- **Animal Safety Dose**: Up to 5 mg/kg/day administered in rodent and pig studies without observed genotoxicity or hepatotoxicity; this does not constitute a recommended human dose.
- **Traditional Crude Extract**: Chelidonium majus latex or whole-plant tinctures containing mixed alkaloids (chelerythrine, sanguinarine, protopine) have been used topically for warts and skin lesions; no standardized chelerythrine percentage for these preparations is established.
- **Human Supplemental Dose**: No established or recommended human dose exists; chelerythrine is not approved or standardized as a nutritional supplement in any major regulatory jurisdiction.
- **Timing and Administration Notes**: Pharmacokinetic data suggest rapid absorption (Cmax <2 h oral) and short half-life (~2.03 h), implying that if future clinical doses are developed, multiple daily administrations may be required to maintain tissue concentrations.

## Safety & Drug Interactions

Chelerythrine exhibits cytotoxicity against normal human cell lines (e.g., HL-7702 hepatocytes) at concentrations of 2.5–20 µM in vitro, suggesting a narrow margin between pharmacologically active and cytotoxic concentrations that has not been resolved in human studies. The quaternary carbon adjacent to the nitrogen is susceptible to nucleophilic attack, which underlies both its receptor-binding potency and its potential for off-target macromolecular damage including DNA adduct formation. Chelerythrine is metabolized via CYP1A pathways, creating potential for pharmacokinetic interactions with CYP1A substrates or inducers such as certain antidepressants, antipsychotics, and caffeine-metabolizing drugs. No use during pregnancy or lactation is advisable given the compound's cytotoxicity, alkaloid nature, and the historical association of greater celandine preparations with hepatotoxicity in case reports; individuals with pre-existing hepatic disease should avoid exposure, and no maximum safe human dose has been formally established.

## Scientific Research

The body of evidence for chelerythrine consists almost entirely of in vitro cell-based assays and animal pharmacokinetic or toxicology studies, with no published large-scale randomized controlled trials in humans. In vitro studies have quantified PKC inhibition (IC50 = 660 nM), BclXL–Bak disruption (IC50 ≈ 1.5 µM), cytotoxicity across cancer and normal cell lines (2.5–20 µM), and antibacterial activity against GBS and Streptococcus suis (MIC 256 µg/mL, MBC 512 µg/mL). Animal pharmacokinetic data from pigs document rapid oral and intramuscular absorption (Cmax within 2 h), a T1/2 of approximately 2.03 h, and rapid [metabolism](/ingredients/condition/weight-management) to dihydrochelerythrine, with no genotoxicity or hepatotoxicity observed at daily doses up to 5 mg/kg. The overall evidence base is preclinical and mechanistic; while findings are biologically plausible and internally consistent, translation to human therapeutic efficacy and safety has not been established.

## Historical & Cultural Context

Chelidonium majus, the primary botanical source of chelerythrine, has a documented history of use spanning over two millennia in European and Asian folk medicine, referenced in ancient Greek, Roman, and medieval herbalist traditions under names such as 'celandine' or 'swallowwort.' Traditional applications centered on its caustic orange latex for removing warts, skin growths, and fungal lesions; internal preparations were historically used for liver, gallbladder, and digestive complaints, though these uses were accompanied by recognized toxicity risks. In Traditional Chinese Medicine, Macleaya cordata (bo luo hui) preparations containing chelerythrine and sanguinarine have been employed for [anti-inflammatory](/ingredients/condition/inflammation) and [antimicrobial](/ingredients/condition/immune-support) purposes, and the plant is approved in China as a feed additive for livestock. The isolation and structural characterization of chelerythrine as a discrete chemical entity in modern pharmaceutical chemistry enabled the transition from crude alkaloid-rich extracts to targeted mechanistic investigation, separating it analytically from co-occurring alkaloids such as sanguinarine that share overlapping but distinct pharmacological profiles.

## Synergistic Combinations

Chelerythrine co-occurs naturally with sanguinarine and protopine in Macleaya cordata extracts, and preclinical antibacterial studies suggest that this alkaloid mixture may produce additive or synergistic membrane-disruption effects against Gram-positive pathogens beyond what isolated chelerythrine achieves alone. In apoptosis-focused research contexts, combining chelerythrine's BclXL–Bak disruption with conventional chemotherapeutic agents targeting distinct pathways (e.g., topoisomerase inhibitors or microtubule stabilizers) is theoretically attractive for reducing individual drug concentrations, though no formal combination index studies in human cells have been published. The G-quadruplex stabilizing activity of chelerythrine could hypothetically complement telomerase inhibitors, since both mechanisms converge on suppressing [telomere](/ingredients/condition/longevity) maintenance in cancer cells, but this synergy remains entirely speculative without supporting experimental data.

## Frequently Asked Questions

### What is chelerythrine and what plant does it come from?

Chelerythrine is a quaternary benzophenanthridine alkaloid (C21H18NO4) found primarily in the orange latex and tissues of Chelidonium majus (greater celandine) and Macleaya cordata (plume poppy). It co-occurs with related alkaloids including sanguinarine and protopine, and has been isolated in purified chloride salt form (≥98% purity) for research use. It is not a nutrient but a pharmacologically active secondary plant metabolite with potent enzyme-inhibiting and membrane-disrupting properties.

### How does chelerythrine work as an anticancer compound?

Chelerythrine inhibits protein kinase C (PKC) with an IC50 of 660 nM, disrupting proliferative signaling, and separately disrupts the BclXL–Bak anti-apoptotic protein interaction (IC50 ≈ 1.5 µM), releasing Bax to trigger intrinsic apoptosis. It also intercalates DNA and stabilizes G-quadruplex structures, which may suppress oncogene expression and telomerase activity. All anticancer evidence is currently from in vitro cell assays (cytotoxicity at 2.5–20 µM against HeLa, A549, and other lines); no human clinical trials have been conducted.

### Is chelerythrine safe for human use or supplementation?

No established safe human dose for chelerythrine exists, and it is not approved as a nutritional supplement in major regulatory jurisdictions. Animal studies indicate tolerability at up to 5 mg/kg/day without genotoxicity or hepatotoxicity, but in vitro data show cytotoxicity against normal liver cells (HL-7702) at 2.5–20 µM, suggesting a narrow therapeutic window. Greater celandine (the primary source plant) has been associated with drug-induced hepatotoxicity in case reports, and chelerythrine should be avoided during pregnancy, lactation, or in individuals with liver disease.

### What are the antibacterial effects of chelerythrine?

Chelerythrine chloride inhibits Group B Streptococcus (GBS) with inhibition zones of 10.76–14.32 mm at 0.5–2 mg/mL and demonstrates MIC and MBC values of 256 µg/mL and 512 µg/mL, respectively, against Streptococcus suis. Its antibacterial mechanism involves disruption of bacterial cell walls and plasma membranes, causing structural collapse, cellular shrinkage, and efflux of ions (Na+, K+, Ca2+, Mg2+) and ATP, achieving bactericidal effects at 2–8× MIC within 24 hours. These findings are from controlled in vitro assays; clinical human data on chelerythrine as an antibiotic agent are absent.

### Does chelerythrine interact with other drugs or medications?

Chelerythrine is metabolized through the CYP1A enzyme system, which could create pharmacokinetic interactions with other CYP1A substrates including certain antipsychotics (e.g., clozapine, olanzapine), antidepressants, theophylline, and caffeine—potentially altering their plasma levels. Its potent PKC inhibition could theoretically interfere with signaling pathways targeted by immunosuppressants or certain kinase-inhibitor drugs. Because human pharmacokinetic and drug interaction studies have not been performed, the full interaction profile is unknown and caution is warranted when combining chelerythrine-containing preparations with any prescription medication.

### What does research show about chelerythrine's effectiveness against cancer cell lines?

In vitro studies demonstrate that chelerythrine induces apoptosis in multiple cancer cell lines including HeLa and A549 cells at concentrations ranging from 2.5–20 µM by disrupting the BclXL–Bak interaction with an IC50 of approximately 1.5 µM. However, these are laboratory findings and do not yet translate to proven clinical efficacy in human patients. Most current evidence comes from cell culture experiments rather than human clinical trials, limiting definitive conclusions about real-world anti-cancer potential.

### How does chelerythrine's mechanism of action compare to conventional protein kinase C inhibitors?

Chelerythrine functions as a potent, cell-permeable PKC inhibitor with an IC50 of 660 nM, making it effective at blocking protein kinase C signaling pathways. Unlike some conventional PKC inhibitors, chelerythrine also triggers apoptosis through direct interaction with anti-apoptotic proteins like BclXL and Bak, providing a dual mechanism of action. This combined approach distinguishes it from single-target PKC inhibitors used in research and clinical settings.

### Who might benefit most from chelerythrine supplementation based on its current research?

Current evidence is primarily limited to laboratory and in vitro research, making it premature to recommend chelerythrine supplementation for specific populations outside of controlled research settings. Individuals interested in alkaloid-based compounds or those participating in clinical trials investigating chelerythrine's anti-cancer properties may be candidates, but general supplementation remains experimental. Consultation with a healthcare provider is essential before considering chelerythrine, particularly given its potent biochemical effects and limited human safety data.

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