Lasiocarpine (Pyrrolizidine Alkaloid · Hepatotoxic · Genotoxic Reference)
| Compound | Lasiocarpine (Heliotrine N-oxide parent; open-chain macrocyclic PA) |
| Class | Alkaloid — Pyrrolizidine (Open-chain diester, retronecine type) |
| CAS | 303-34-4 |
| Molecular formula | C₂₁H₃₃NO₇ |
| Primary sources | Heliotropium europaeum, Heliotropium lasiocarpum, Symphytum officinale (minor) |
| Plant part | Aerial parts, seeds |
| Claim strength | Emerging (toxicology) |
| Key applications | EFSA priority PA; hepatotoxicity research; carcinogenicity reference; informational-only |
| Buy from Herbuno | Informational reference — see HerbIQ Compound Index → |
Name origin: Lasiocarpine is named after Heliotropium lasiocarpum (lasio = hairy, carpum = fruit), a Mediterranean and Middle Eastern Heliotropium species responsible for livestock and human PA poisoning in semiarid regions. Heliotropium europaeum (common heliotrope, tarn weed) is the most important agricultural source of lasiocarpine in European and Australian livestock contexts. Traditional context: Heliotropium species have no beneficial traditional medicinal use — their history is as poisonous weeds responsible for livestock losses and hepatic veno-occlusive disease outbreaks in humans consuming contaminated grain (historical epidemics in Afghanistan, Tajikistan, and India). Certain Heliotropium species were used in folk medicine for skin conditions, but their hepatotoxic PA content precludes any legitimate supplement application. Research trajectory: Lasiocarpine is one of the six EFSA priority PAs selected for quantitative risk assessment due to their high hepatotoxic potency and potential human exposure via grain, honey, and herbal supplement contamination. It is among the most genotoxically potent PAs identified. Safety context: Lasiocarpine is a confirmed human hepatotoxin and probable carcinogen (IARC Group 2B). Its CYP3A4-mediated metabolic activation produces highly reactive pyrrolic species with stronger DNA crosslinking activity than many other PA congeners.
Toxicological Profile of Lasiocarpine
Hepatotoxicity: Lasiocarpine is among the most acutely hepatotoxic PAs studied — rodent oral LD₅₀ values of 70–150 mg/kg are lower than most other PAs. Its open-chain diester structure (rather than macrocyclic) increases aqueous solubility and GI absorption relative to macrocyclic PAs. CYP3A4 oxidation to dehydrolasiocarpine pyrrole creates a potent bifunctional alkylator that crosslinks hepatocyte DNA. Claim strength: High (toxicology).
Carcinogenicity: Lasiocarpine has been classified as a possible human carcinogen (IARC Group 2B) based on sufficient evidence of carcinogenicity in rodent studies — liver tumours in rats and mice at sub-hepatotoxic chronic doses. The WHO/EFSA genotoxicity assessment places lasiocarpine among the PAs of highest concern for human cancer risk from food and supplement contamination. Claim strength: High (toxicology/regulatory).
EFSA priority status: EFSA's 2016 and 2022 scientific opinions identify lasiocarpine, senecionine, retrorsine, echimidine, heliotrine, and lycopsamine as priority PAs for monitoring in food and botanical products. Lasiocarpine's particular potency and presence in Heliotropium (a common grain contaminant in Mediterranean and Central Asian agriculture) makes it a priority analytical target. Claim strength: High (regulatory).
Grain and honey contamination: Lasiocarpine is identified as a significant contaminant risk in: grain (from Heliotropium weed seed co-harvest), honey (from Heliotropium nectar foraging), pollen supplements (from Heliotropium-contaminated pastures), and botanical herbal teas when Heliotropium grows as a weed in collection areas. Claim strength: High (food safety).
This compound is documented for research and formulator education purposes. For commercially available botanical ingredients, explore the HerbIQ Compound Index →
Regulatory and Safety Context for Formulators
Lasiocarpine is the highest-priority PA for analytical screening in botanical product quality assurance. Its detection at any concentration in food supplement raw materials should trigger supply chain review — the presence of lasiocarpine indicates Heliotropium contamination, which also brings other Heliotropium-associated PAs (heliotrine, europine, acetylheliotrine).
EU Regulation 2020/2040 sets maximum levels for lasiocarpine and heliotrine in honey (0.1 μg/kg combined), herbal infusions (0.35 μg/kg), food supplements (1.0 μg/kg for adults), and pollen products. These limits reflect EFSA's MOE analysis and represent the strictest PA-specific limits yet established in food law.
Botanicals with highest lasiocarpine contamination risk: borage seed (Mediterranean-sourced), honey from Mediterranean, Middle Eastern, and Australian regions; grain products from Afghanistan, India, and North Africa. Botanical raw material CoAs should include lasiocarpine in the PA screening panel (minimum 28-PA EFSA panel by LC-MS/MS).
There is no therapeutic antidote for lasiocarpine poisoning. Clinical management of PA-induced sinusoidal obstruction syndrome is supportive, with defibrotide showing efficacy in haematopoietic stem cell transplant-related VOD (which shares the PA hepatotoxicity mechanism). Early detection and cessation of exposure is the only preventive intervention.
Frequently Asked Questions — Lasiocarpine
Why is lasiocarpine specifically among the most toxic pyrrolizidine alkaloids?
PA hepatotoxicity correlates with the ability of CYP enzymes to generate reactive pyrrolic esters and with the electrophilic reactivity of these species toward DNA. Lasiocarpine's open-chain diester structure, combined with the retronecine necine base (which is efficiently oxidised by CYP3A4), produces highly reactive dehydrolasiocarpine with strong DNA crosslinking activity. Its higher water solubility versus macrocyclic PAs also enhances GI absorption — increasing the systemic dose reaching the liver for activation.
How is lasiocarpine different from senecionine and other macrocyclic PAs?
Lasiocarpine is an open-chain diester PA (two separate ester linkages connecting the necine base to necic acids), while senecionine and retrorsine are macrocyclic PAs (two ester linkages forming a ring). Macrocyclic PAs tend to be less water-soluble but can have equal or greater toxicity depending on CYP activation efficiency. EFSA risk assessment treats the full PA class with a group approach, but lasiocarpine's potency within the class is particularly high.
What Heliotropium-contaminated agricultural products should formulators screen?
Formulators using Mediterranean or Central Asian-origin honey, borage seed oil, grain-based ingredients, or pollen should require lasiocarpine-specific testing in the EFSA 28-PA LC-MS/MS panel. Honey and pollen are particularly high-risk when sourcing from regions where Heliotropium europaeum and H. lasiocarpum grow as agricultural weeds. Certificate of Analysis documentation should include PA results to applicable EU limits.
Is comfrey (Symphytum) a significant source of lasiocarpine?
Comfrey contains primarily symphytine, echimidine, and their N-oxides; lasiocarpine is not the dominant PA in Symphytum. Comfrey's hepatotoxic PA concern centres on symphytine and echimidine, which are Symphytum-specific. Lasiocarpine at low concentrations has been detected in some comfrey samples but is not characteristically a Symphytum alkaloid — the Heliotropium genus is the primary commercial contamination source for lasiocarpine specifically.
Related compounds: Retrorsine, Lycopsamine, Senkirkine, Platyphylline
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
← HerbIQ Compound Index · HerbIQ P02: Extraction · HerbIQ P03: Delivery