Lactucin

Lactucin at a Glance

Lactucin is a guaianolide sesquiterpene lactone — the principal bitter molecule of lactucarium, the dried milky latex of wild lettuce (Lactuca virosa) and its relatives. It is a large part of why a bolted lettuce, an endive or a chicory root tastes bitter, and it is the compound that carries most of the pharmacological reputation of “lettuce opium” ^{1,3Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}.

That reputation needs handling carefully, and it is handled up front. Lactucin is not an opioid, is not chemically related to one, and lactucarium contains no opiate alkaloids. The nickname is a 19th-century materia-medica accident, not a chemical description ^{19Reference 19Trojanowska A · 2005ReviewLettuce (Lactuca sp.) as a medicinal plant in Polish publications of the 19th century — historical reviewView study →}. What is real is a small, consistent preclinical signal: isolated lactucin is analgesic and sedative in mice at 15–30 mg/kg ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}, it displaces the benzodiazepine-site radioligand [³H]-flumazenil from GABA-A receptors ^{2Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →}, and it is a potent anti-neuroinflammatory agent in cultured cells ^{6Reference 6Wei Z et al. · 2024In vitroGuaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities — in vitroView study →}. Since 2020 the most active research has actually moved away from the nervous system entirely, toward the liver and metabolism ^{7,8,9Reference 7Qin D et al. · 2024AnimalLactucin reverses liver fibrosis by inhibiting TGF-β1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism — animal in vivoView study →Reference 8Zhu L et al. · 2025AnimalLactucin alleviates liver fibrosis by regulating the TLR4-MyD88-MAPK/NF-κB signaling pathway through intestinal flora — animal in vivoView study →Reference 9Zhong Y et al. · 2025AnimalLactucin and lactucopicrin ameliorate obesity in high-fat diet fed mice by promoting white adipose tissue browning through activation of the AMPK/SIRT1/PGC-1α pathway — animal in vivoView study →}.

Two structural facts govern everything below. First, the plant does not store free lactucin — it stores oxalate and sulfate conjugates in the latex, and the free molecule most chemistry has studied is largely liberated by wounding, drying and extraction ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}. Second, lactucin’s reactive α-methylene-γ-lactone group — the shared warhead of the sesquiterpene-lactone class — is hydrogenated by human gut bacteria before absorption, which is a serious problem for reading its in-vitro pharmacology onto a salad ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}.

”Lettuce Opium”: Myth vs. Evidence

The claim that dried lettuce latex is a mild opium substitute is genuinely old and genuinely well documented — as a belief. Nineteenth-century Polish medical literature reviewed by Trojanowska records lactucarium as an intoxicant used as a sedative and analgesic, described as weaker than opium but free of its side-effects, with practitioners reporting that in some cases it worked better ^{19Reference 19Trojanowska A · 2005ReviewLettuce (Lactuca sp.) as a medicinal plant in Polish publications of the 19th century — historical reviewView study →}. That same historical review records the crucial epilogue: contemporary chemists set out to identify the substance responsible and failed ^{19Reference 19Trojanowska A · 2005ReviewLettuce (Lactuca sp.) as a medicinal plant in Polish publications of the 19th century — historical reviewView study →}. The reputation arrived first; the chemistry never caught up with it.

Here is the honest ledger.

What is myth. That lactucarium contains an opiate, acts on opioid receptors, or is pharmacologically a “natural opium.” None of these is true. There is no opiate alkaloid in Lactuca, and no opioid-receptor activity has been published for lactucin. The name is the entire basis of the claim.

What is untested. Essentially the whole traditional use. There is no controlled study of lactucarium, none of Lactuca virosa, and no clinical trial of lactucin. The two small human sleep trials that circulate in this literature used Lactuca sativa seed oil — a different plant part of a different species, with no meaningful sesquiterpene-lactone content — so they are not evidence for lactucin at all.

What is real, at the preclinical tier. Wesołowska and colleagues tested lactucin, lactucopicrin and 11β,13-dihydrolactucin side by side in mice and found all three analgesic in hot-plate and tail-flick tests at 15 and 30 mg/kg, comparable to ibuprofen at 30–60 mg/kg — and found lactucin and lactucopicrin, but not 11β,13-dihydrolactucin, sedative in the spontaneous-locomotor test ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}. That single 2006 paper is still the strongest direct support the traditional claim has, and it is a mouse study of purified compounds, not of lactucarium.

The consolation prize. Tradition was directionally right about the class — bitter guaianolides, not opiates, are what carry wild lettuce’s sedative and analgesic reputation. It was wrong about the mechanism, wrong about the comparison to opium, and it has never been checked in a person.

The Conjugate Problem: What the Plant Actually Stores

Most of the lactucin literature quietly assumes the molecule exists in the plant as drawn. It largely does not.

Sessa and colleagues profiled Lactuca latex directly and found that its major components are 15-oxalyl and 8-sulfate conjugates of lactucin, deoxylactucin and lactucopicrin — not the free lactones ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}. The oxalates are unstable and revert to the parent sesquiterpene lactone on hydrolysis; the sulfates are stable, and were the first sesquiterpene sulfates reported from any plant ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}. Chicory latex carries the oxalyl conjugates but, notably, lacks the 8-sulfates ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}. Conjugate proportions also shift with developmental stage ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}, and chicory work confirms the same picture — the guaianolides accumulate in taproot latex predominantly in oxalated forms ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}.

Three consequences follow, and they shape everything that comes after:

• Free lactucin is substantially a preparation artifact. Wounding, drying and solvent extraction hydrolyse the labile oxalates. The lactucarium of the old materia medica, and the “lactucin content” of a modern extract assay, are both partly made by the process that measures them.
• Species and cultivar profiles are not interchangeable. Sesquiterpene-lactone profiles vary substantially between lettuce varieties and between Lactuca species ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}, and stem-chicory transcriptome and metabolite work shows the pathway is under real genetic and developmental control ^{38Reference 38Testone G et al. · 2016In vitroInsights into the sesquiterpenoid pathway by metabolic profiling and de novo transcriptome assembly of stem-chicory (Cichorium intybus cultigroup “Catalogna”) — in vitroView study →}. A figure from romaine lettuce does not transfer to L. virosa.
• The conjugates are themselves the story of lettuce bitterness. Sessa’s group explicitly proposed these constitutive lactones as the molecular basis of the bitter taste of lettuce and related species, and found no correlation with pathogen resistance ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →} — which reframes lactucin as a taste compound with pharmacology attached rather than a defence toxin.

Lactucin-8-sulfate has its own entry as a distinct latex constituent for exactly this reason.

The Michael-Acceptor Warhead — and What the Gut Does to It

Lactucin does carry the exocyclic α-methylene-γ-lactone group. This is not an assumption: the existence of 11β,13-dihydrolactucin as a separately named, separately tested compound in the same 2006 study defines lactucin as the unreduced parent ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}, and gut-microbiota work recovers tetrahydrolactucin and hexahydrolactucin from lactucin through “double bond hydrogenations,” which requires the double bond to have been there ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}.

That group is a Michael acceptor. It alkylates cysteine thiols, and it is the shared reason most sesquiterpene lactones inhibit NF-κB, engage Keap1/Nrf2, and show broad cytotoxicity across unrelated cell lines. This is a class property, not a lactucin property. When you read that lactucin suppresses NF-κB, downregulates BCL-2, or kills a cancer cell line at micromolar concentrations, the correct first hypothesis is thiol alkylation shared with parthenolide, costunolide and several hundred other lactones — which is also why such compounds are usually poorly selective. Class reactivity is labelled as class reactivity.

The genuinely lactucin-specific claims are narrower and worth separating out:

• Sedation. Lactucin and lactucopicrin are sedative in mice; 11β,13-dihydrolactucin — the same molecule with the warhead reduced — is analgesic but not sedative ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}. That dissociation is a real structure–activity result, and it points the wrong way for a pure thiol-alkylation story: the reduced compound keeps analgesia and loses sedation.
• The GABA-A interaction, which is a binding-site phenomenon rather than an alkylation one ^{2Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →}.
• Potency at low micromolar in a neuroinflammation assay (IC₅₀ 1.82 µM), where lactucin was one of only four actives among twenty guaianolides tested — meaning most of the class, warhead and all, was inactive in that assay ^{6Reference 6Wei Z et al. · 2024In vitroGuaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities — in vitroView study →}.

And the sting in the tail: the human gut microbiota hydrogenates the α-methylene double bond before absorption ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}. Whatever the warhead does in a dish, it is chemically disarmed on the way in.

What It's Used For

Lactucin sits entirely in the preclinical tier. The evidence has two distinct halves: an older, thinner neuropharmacology literature that carries the traditional reputation, and a much more active post-2020 body of hepatic and metabolic work — most of it in mice, all of it using the isolated molecule, and most of it converging on AMPK/SIRT1 signalling rather than on anything to do with sedation.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric, and I’ll keep honing the formula over time. Each application name links down to its write-up.

01Sedative & sleep supportPromising55%One mouse locomotor study of the isolate + [³H]-flumazenil displacement + replicated rodent sleep work on lettuce extracts; no human data on lactucin.

02Liver protectionPromising50%Two mouse fibrosis models with mechanism (TGF-β1/STAT3; TLR4-MyD88 via gut flora), plus three hepatocyte steatosis papers.

03AnalgesiaPromising48%A single 2006 mouse study — hot-plate and tail-flick at 15–30 mg/kg, ibuprofen-comparable; strong tradition, no dose–response, no human data.

04Metabolic & adiposity effectsPromising45%White-adipose browning in high-fat-diet mice; adipogenesis and myotube glucose-uptake work otherwise in vitro.

05Anti-neuroinflammatory activityShaky42%One phytochemistry screen, IC₅₀ 1.82 µM in cultured cells; no animal neuroinflammation model.

06AnticancerShaky38%Gastric-cancer mouse xenograft plus scattered single-cell-line work; the mechanisms are generic to the lactone class.

07AntimalarialShaky28%One in-vitro Plasmodium falciparum assay of chicory-derived lactucin and lactucopicrin.

Mechanisms

The last row is included deliberately. The acetylcholinesterase story that circulates for chicory and wild lettuce belongs to lactucopicrin and 8-deoxylactucin, not to lactucin — and even for them the inhibitory concentrations are high ^{23,24Reference 23Rollinger JM et al. · 2005In vitroApplication of the in combo screening approach for the discovery of non-alkaloid acetylcholinesterase inhibitors from Cichorium intybus — in vitroView study →Reference 24Jaśkiewicz A et al. · 2022In vitroEvaluation of activity of sesquiterpene lactones and chicory extracts as acetylcholinesterase inhibitors assayed in calorimetric and docking simulation studies — in vitroView study →}.

Pharmacokinetics

This is the most important section on the page and the one that constrains everything above.

Absorption and microbial transformation. García and colleagues performed the first study of human gut-microbiota metabolism of dietary sesquiterpene lactones, fermenting lactucin, lactucopicrin and romaine lettuce with faecal microbiota from independent donors ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}. The dominant reactions were dehydroxylations and double-bond hydrogenations. Lactucin yielded tetrahydrolactucin and hexahydrolactucin — meaning the α-methylene group that drives the compound’s in-vitro reactivity is reduced away before absorption ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}.

Human exposure is to metabolites, not to lactucin. In healthy volunteers who ate escarole salad, urine contained glucuronide and sulfate conjugates of dihydrolactucopicrin, tetrahydrolactucopicrin, dihydrolactucin and deoxylactucin — the reduced, phase-II–conjugated products — with large inter-subject variability tracking differences in gut microbiota composition ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}. That variability is a pharmacological finding in its own right: the same salad delivers different metabolite profiles to different people.

Why this matters. The mouse studies dose lactucin directly at 15–30 mg/kg and above, bypassing or overwhelming this transformation; in-vitro work applies the intact molecule at micromolar concentrations. Neither reflects what reaches a person’s circulation from food. And the one structure–activity result available is not reassuring for the reduced forms: 11β,13-dihydrolactucin — the mono-reduced analogue — lost the sedative effect that lactucin retained ^{1Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}. If the gut performs that reduction and more, the sedative pharmacology of a dietary or oral herbal exposure is genuinely in doubt.

Not characterised for lactucin: oral bioavailability (no figure exists), plasma Cmax or half-life, protein binding, brain penetration, CYP interactions, or transporter substrate status. The molecule is also photolabile ^{18,33Reference 18Bischoff TA et al. · 2004In vitroAntimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus L. — in vitroView study →Reference 33Schenck G et al. · 1964Studies on the photochemical transformation of lactucin — laboratory studyView study →}, so preparation and storage affect what is actually administered.

Clinical Trials

No registered clinical trial has tested lactucin, lactucarium, or Lactuca virosa in humans. The only human data touching this molecule at all is the escarole-salad metabolite study, which measured urinary metabolites and no clinical endpoint ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

The split here is unusually clean, and unusually important, because the plant reputation and the molecule evidence come from different centuries and different species.

Isolate studies dominate the pharmacology. Every claim in the Pharmacology section above — sedation, analgesia, GABA-A binding, liver fibrosis, adipose browning, neuroinflammation, cytotoxicity, antimalarial activity — used purified lactucin ^{1,6,7,8,9,10,11,15,16,17,18Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →Reference 6Wei Z et al. · 2024In vitroGuaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities — in vitroView study →Reference 7Qin D et al. · 2024AnimalLactucin reverses liver fibrosis by inhibiting TGF-β1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism — animal in vivoView study →Reference 8Zhu L et al. · 2025AnimalLactucin alleviates liver fibrosis by regulating the TLR4-MyD88-MAPK/NF-κB signaling pathway through intestinal flora — animal in vivoView study →Reference 9Zhong Y et al. · 2025AnimalLactucin and lactucopicrin ameliorate obesity in high-fat diet fed mice by promoting white adipose tissue browning through activation of the AMPK/SIRT1/PGC-1α pathway — animal in vivoView study →Reference 10Wang X et al. · 2020In vitroA potential nutraceutical candidate lactucin inhibits adipogenesis through downregulation of JAK2/STAT3 signaling pathway-mediated mitotic clonal expansion — in vitroView study →Reference 11Zheng H et al. · 2025In vitroLactucin enhances glucose uptake and glycolysis in C2C12 myotubes by activating AMPK signaling pathway — in vitroView study →Reference 15Wei D et al. · 2026AnimalLactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling — animal in vivo (xenograft)View study →Reference 16Imam KMSU et al. · 2022In vitroLactucin, a bitter sesquiterpene from Cichorium intybus, inhibits cancer cell proliferation by downregulating the MAPK and central carbon metabolism pathway — in vitroView study →Reference 17Jang JH et al. · 2021In vitroLactucin induces apoptosis through reactive oxygen species-mediated BCL-2 and CFLAR(L) downregulation in Caki-1 cells — in vitroView study →Reference 18Bischoff TA et al. · 2004In vitroAntimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus L. — in vitroView study →}. That is normally a strength on a molecule page. Here it comes with a species problem: the purified material was overwhelmingly sourced from chicory (Cichorium intybus), glandular chicory (C. glandulosum) or garden lettuce (L. sativa), not from L. virosa ^{6,15,16,18Reference 6Wei Z et al. · 2024In vitroGuaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities — in vitroView study →Reference 15Wei D et al. · 2026AnimalLactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling — animal in vivo (xenograft)View study →Reference 16Imam KMSU et al. · 2022In vitroLactucin, a bitter sesquiterpene from Cichorium intybus, inhibits cancer cell proliferation by downregulating the MAPK and central carbon metabolism pathway — in vitroView study →Reference 18Bischoff TA et al. · 2004In vitroAntimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus L. — in vitroView study →}. The molecule is the same; the plants are not, and none of it transfers to a wild-lettuce preparation’s other constituents, dose or ratio.

Plant studies are almost all garden lettuce. The GABA-A/sleep replication set — flumazenil-reversible sleep promotion, adenosine A1 upregulation, caffeine-insomnia reversal — is Lactuca sativa leaf extract standardised on lactucin and lactucopicrin content ^{2,20,21,22Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →Reference 20Ahn Y et al. · 2023AnimalHeukharang lettuce (Lactuca sativa L.) leaf extract displays sleep-promoting effects through GABA-A receptor — animal in vivoView study →Reference 21Lee M et al. · 2024AnimalLactuca sativa L. extract enhances sleep duration through upregulation of adenosine A1 receptor and GABA-A receptor subunits in pentobarbital-injected mice — animal in vivoView study →Reference 22Kim HD et al. · 2017AnimalSleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep — animal in vivoView study →}. These are the best causal evidence that lactucin-containing material is sedative in a whole animal, and they are also, precisely, not studies of wild lettuce or lactucarium.

Nothing tests the traditional article. There is no controlled study of lactucarium — the dried latex, the actual historical preparation — in any species. Given that the latex stores lactucin mainly as labile oxalate and stable sulfate conjugates ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}, lactucarium is not simply “lactucin, dried”; its composition depends on how it was collected and dried, and it has never been characterised pharmacologically.

Transferability verdict: weak in both directions. A mouse given 30 mg/kg purified lactucin is not a model of a person drinking wild-lettuce tea, and a romaine-lettuce extract’s sleep effect is not proof that any given lactucarium preparation does the same thing.

Prevalence in Nature

Lactucin is a latex compound of the Cichorieae tribe within Asteraceae — the lettuce/chicory/dandelion lineage — and it is functionally a taste and deterrence molecule rather than a trace metabolite.

Principal sources. Lactuca virosa and Lactuca sativa, in the milky latex of stems and leaves ^{1,3Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}, and Cichorium intybus, chiefly in taproot latex ^{5,18Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →Reference 18Bischoff TA et al. · 2004In vitroAntimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus L. — in vitroView study →}. It also occurs in Cichorium glandulosum ^{6Reference 6Wei Z et al. · 2024In vitroGuaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities — in vitroView study →}, Cichorium pumilum ^{36Reference 36Kisiel W · 2003In vitroRoot constituents of Cichorium pumilum and rearrangements of some lactucin-like guaianolides — in vitroView study →}, and in Picris conyzoides, where lactucin-type glycosides have been characterised ^{37Reference 37Michalska K et al. · 2011Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides — laboratory studyView study →}. Escarole and endive (C. endivia) deliver measurable amounts in the diet — enough for urinary metabolites to be detectable after a single salad ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}.

Concentrations. Reliable figures are scarce, and none exists for L. virosa itself. The best-anchored number is from a green romaine L. sativa extract, assayed at ~1,072 µg/g lactucin against ~199 µg/g lactucopicrin — a roughly 5:1 ratio favouring lactucin ^{2Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →}. That figure is for an extract, not fresh tissue, and cannot be read as a plant content. Content varies substantially between lettuce varieties, between Lactuca species, and with developmental stage ^{3,38Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →Reference 38Testone G et al. · 2016In vitroInsights into the sesquiterpenoid pathway by metabolic profiling and de novo transcriptome assembly of stem-chicory (Cichorium intybus cultigroup “Catalogna”) — in vitroView study →}, and — because the plant stores conjugates — measured “lactucin” partly reflects how much oxalate hydrolysed during workup ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}. Treat all L. virosa figures as no-data.

Beyond plants. A structural relative, 3,4-dihydro-lactucin, has been isolated from the actinomycete Microbispora rosea ^{35Reference 35Taechowisan T et al. · 2024In vitroApoptotic potential and molecular docking of 3,4-dihydro-lactucin, a compound with anticancer properties derived from Microbispora rosea AL22 — in vitroView study →} — a reminder that guaianolide-type scaffolds are not exclusively higher-plant chemistry.

Its role in the plant. Lactucin sits at the end of the guaianolide branch of the sesquiterpene pathway: germacrene A synthase opens the route, and silencing those genes reduces guaianolide oxalate content in chicory ^{30Reference 30Bogdanović M et al. · 2020In vitroSilencing of germacrene A synthase genes reduces guaianolide oxalate content in Cichorium intybus L. — in vitroView study →}; the final regiospecific hydroxylation of 8-deoxylactucin to lactucin is performed by the cytochrome P450 CYP71DD33, identified as chicory’s lactucin synthase by CRISPR/Cas9 knockout ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}. That gene is expressed predominantly in the latex — meaning the late steps of the pathway happen in the very tissue that gets exuded when the plant is wounded ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}. Functionally, the evidence points to taste and deterrence rather than pathogen defence: the constitutive lactones did not correlate with disease resistance, but were proposed as the molecular basis of lettuce bitterness ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}.

Why breeders care. That bitterness makes lactucin an explicit crop-improvement target, and the direction of travel is away from it. Knocking out CYP71DD33 in chicory almost completely eliminated lactucin and lactucopicrin and their oxalates, and correspondingly boosted 8-deoxylactucin and its derivatives — which the same group showed to have anti-inflammatory activity in an inflamed intestinal-mucosa model ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}. Root chicory is being positioned as a crop from which different health-product fractions can be extracted ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}, so the lactucin content of commercial chicory is now a deliberate breeding decision rather than a fixed botanical fact.

Discovery & Synthesis

First isolation. Lactucin belongs to the 19th-century lactucarium literature, when chemists were explicitly trying to find the substance responsible for lettuce latex’s sedative reputation — an effort the historical record describes as having failed to produce the expected results ^{19Reference 19Trojanowska A · 2005ReviewLettuce (Lactuca sp.) as a medicinal plant in Polish publications of the 19th century — historical reviewView study →}. A precise first-isolation attribution is not verified here and should be treated as open.

Modern preparative chemistry. The reproducible route dates to Schenck and co-workers, who published on the preparation of lactucin and lactucopicrin from Lactuca virosa plants in 1961, as part of a series on the enzymatic and non-enzymatic oxidation of therapeutically active plant substances ^{32Reference 32Schenck G et al. · 1961Research on the preparation of lactucin and lactucopicrin from Lactuca virosa plants (15: on the enzymatic and non-enzymatic oxidation of therapeutically active plant substances) — laboratory methodView study →}. The same group established lactucin’s photochemical transformation in 1964 ^{33Reference 33Schenck G et al. · 1964Studies on the photochemical transformation of lactucin — laboratory studyView study →} — the earliest documentation of the light sensitivity that still complicates its handling. Structural work continued through NMR characterisation of lactucin-type guaianolides and their glycosides, and through the rearrangement chemistry that defines the lactucin skeleton ^{36,37Reference 36Kisiel W · 2003In vitroRoot constituents of Cichorium pumilum and rearrangements of some lactucin-like guaianolides — in vitroView study →Reference 37Michalska K et al. · 2011Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides — laboratory studyView study →}.

Total synthesis. No total synthesis of lactucin is documented in the literature surveyed. Given the guaianolide’s stereochemical density and the reactive exocyclic methylene, that is unsurprising; the field has gone to plants instead.

Manufacture today. Supply is by extraction and semi-synthesis from chicory, not by synthesis. A three-step process published in 2023 isolates gram-scale quantities of bioactive sesquiterpene lactones from Cichorium intybus roots and derives semisynthetic chicory STL standards from them ^{31Reference 31Ruggieri F et al. · 2023A three-step process to isolate large quantities of bioactive sesquiterpene lactones from Cichorium intybus L. roots and semisynthesis of chicory STL standards — laboratory methodView study →}; supercritical-fluid extraction of chicory STL fractions is used for the bioactivity work ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}. Chicory root is the practical source for everything — reference standards, screening material, and the extract fractions being developed commercially. Metabolic engineering of the chicory pathway is an active alternative, running in both directions: silencing germacrene A synthase to reduce guaianolides ^{30Reference 30Bogdanović M et al. · 2020In vitroSilencing of germacrene A synthase genes reduces guaianolide oxalate content in Cichorium intybus L. — in vitroView study →}, or knocking out lactucin synthase to redirect flux to 8-deoxylactucin ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}.

Patents: not yet researched.

Toxicity & Safety

Direct toxicology on isolated lactucin is essentially absent. No LD₅₀, no repeat-dose study, no genotoxicity package, and no reproductive-toxicity dataset for the pure compound was located. The “low” rating here reflects dietary reassurance — lactucin is consumed routinely in lettuce, endive, escarole and chicory, and human volunteers eating escarole salad showed only ordinary metabolite excretion ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →} — not a characterised safety profile for the isolate. Do not read silence as safety.

The Plant Is Not as Benign as the Molecule

The overdose signal belongs to wild lettuce, not to lactucin, and it is real. A case report documents Lactuca virosa toxicity requiring hospital care ^{28Reference 28Besharat S et al. · 2009Case reportWild lettuce (Lactuca virosa) toxicity — case reportView study →}, and a French report describes abuse of L. virosa ^{29Reference 29Spadari M et al. · 2003Case reportAbuse of Lactuca virosa — case reportView study →}. Presentations in this literature involve agitation, dizziness, nausea and anticholinergic-type CNS effects. Nothing attributes these to lactucin specifically — lactucarium is a complex, unstandardised latex — but they are why concentrated wild-lettuce preparations warrant more caution than the “gentle sedative” framing suggests.

Sedation & Its Interactions

Lactucin’s sedative activity is benzodiazepine-site–linked ^{1,2Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →}, so the expected interaction class is additive CNS depression — benzodiazepines, Z-drugs, barbiturates, opioids, sedating antihistamines, alcohol. This is a mechanistic inference from the binding data, not a documented human interaction: no clinical interaction study exists, and no CYP-isoform or P-glycoprotein data have been generated for lactucin at all. Driving and machinery cautions follow from the mechanism rather than from a case record.

Asteraceae Contact Dermatitis

Lettuce contact allergy is documented, mostly occupational, and mostly in handlers rather than eaters. Aimed patch testing in Compositae-allergic patients found positive lettuce reactions in 11% and 22% across two Danish studies, with most cases non-occupational and partly attributable to cross-reactivity ^{26Reference 26Paulsen E · 2016ReviewLettuce contact allergy — reviewView study →}. Sesquiterpene lactones are the recognised Compositae hapten class, and systemic allergic dermatitis after ingestion is proven most convincingly for strong allergens such as costunolide in bay leaves and less so for the weak allergens of lettuce ^{27Reference 27Paulsen E · 2017ReviewSystemic allergic dermatitis caused by sesquiterpene lactones — reviewView study →} — so lettuce lactones, lactucin included, are best described as weak sensitisers.

The screening trap matters here. The standard sesquiterpene lactone (SL) mix patch reagent contains only three haptens — alantolactone, costunolide and dehydrocostus lactone ^{25Reference 25Paulsen E et al. · 2001Clinical trialSensitization and cross-reaction patterns in Danish Compositae-allergic patients — clinical studyView study →} — and lactucin is not one of them. The lettuce-allergy review is explicit that SL mix is a poor screening agent for lettuce contact allergy, with positive reactions significantly more common in non-occupationally sensitised patients, and recommends patch testing with freshly cut lettuce stem supplemented by Compositae mix instead, because lettuce allergens degrade easily ^{26Reference 26Paulsen E · 2016ReviewLettuce contact allergy — reviewView study →}. A negative SL-mix patch test does not exclude sensitivity to lettuce or to lactucin. Prick-to-prick testing is also advised, since contact urticaria and protein contact dermatitis can present as dermatitis ^{26Reference 26Paulsen E · 2016ReviewLettuce contact allergy — reviewView study →}.

I could not locate a study attributing lettuce patch-test positivity to lactucin as an individual hapten; the class attribution is solid, the molecule-level attribution is not.

Safety at a Glance

✅ Low / no toxicityAllergy riskSedating

• Ordinary dietary exposure is well tolerated. Lactucin is a normal constituent of lettuce, endive, escarole and chicory root; human volunteers show only routine metabolite excretion after a salad ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}.
• Additive sedation is the predictable interaction. Benzodiazepine-site activity means CNS depressants, alcohol and sedating medications should be treated as additive — inferred from mechanism, never tested in humans ^{1,2Reference 1Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →Reference 2Kim HW et al. · 2019AnimalEffectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivoView study →}.
• Concentrated wild-lettuce preparations have their own overdose record. Case reports document toxicity and abuse of Lactuca virosa, with agitation and CNS effects; this is a plant-level signal, not a lactucin one ^{28,29Reference 28Besharat S et al. · 2009Case reportWild lettuce (Lactuca virosa) toxicity — case reportView study →Reference 29Spadari M et al. · 2003Case reportAbuse of Lactuca virosa — case reportView study →}.
• Asteraceae contact allergy — and the SL-mix test will not rule it out. The standard SL mix contains alantolactone, costunolide and dehydrocostus lactone only; a negative result does not exclude lettuce or lactucin sensitivity ^{25,26Reference 25Paulsen E et al. · 2001Clinical trialSensitization and cross-reaction patterns in Danish Compositae-allergic patients — clinical studyView study →Reference 26Paulsen E · 2016ReviewLettuce contact allergy — reviewView study →}.
• No isolate toxicology exists. No LD₅₀, repeat-dose, genotoxicity, reproductive or CYP/transporter data for pure lactucin. The low rating rests on dietary history, not on testing.

Dosage

There is no established human dose for lactucin, and none is offered. No clinical trial has administered it, no oral bioavailability figure exists, and the gut microbiota chemically alters the molecule before absorption ^{4Reference 4García CJ et al. · 2020Clinical trialHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteersView study →}. Everything below is a research figure reported in the cited studies, listed so the numbers here can be read in context.

Human exposure, for scale. The realistic routes are dietary — bitter lettuces, endive, escarole, chicory root and roasted chicory — plus traditional wild-lettuce tea, tincture or lactucarium, none of which is standardised for lactucin content. Because the plant stores lactucin as conjugates whose hydrolysis depends on handling ^{3Reference 3Sessa RA et al. · 2000In vitroMetabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitroView study →}, and because chicory lactucin content is now a deliberate breeding variable ^{5Reference 5Cankar K et al. · 2023In vitroLactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitroView study →}, two nominally identical preparations can differ substantially.

These are doses studied in research and are not a personal recommendation.

References

1. Wesołowska A, Nikiforuk A, Michalska K, Kisiel W, Chojnacka-Wójcik E (2006). Analgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivo. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/16621374/
2. Kim HW, Suh HJ, Choi HS, Hong KB, Jo K (2019). Effectiveness of the sleep enhancement by green romaine lettuce (Lactuca sativa) in a rodent model — animal in vivo. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/31582660/
3. Sessa RA, Bennett MH, Lewis MJ, Mansfield JW, Beale MH (2000). Metabolite profiling of sesquiterpene lactones from Lactuca species: major latex components are novel oxalate and sulfate conjugates of lactucin and its derivatives — in vitro. Journal of Biological Chemistry. https://pubmed.ncbi.nlm.nih.gov/10858433/
4. García CJ, Beltrán D, Tomás-Barberán FA (2020). Human gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivo — human volunteers. Molecular Nutrition & Food Research. https://pubmed.ncbi.nlm.nih.gov/32970341/
5. Cankar K, Hakkert JC, Sevenier R, et al. (2023). Lactucin synthase inactivation boosts the accumulation of anti-inflammatory 8-deoxylactucin and its derivatives in chicory (Cichorium intybus L.) — in vitro. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/37036799/
6. Wei Z, Turak A, Li B, Aisa HA (2024). Guaianolide sesquiterpene lactones from Cichorium glandulosum and their anti-neuroinflammation activities — in vitro. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/39032793/
7. Qin D, Han C, Gao Y, Li H, Zhu L (2024). Lactucin reverses liver fibrosis by inhibiting TGF-β1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism — animal in vivo. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/39164375/
8. Zhu L, Lv B, Gao Y, Qin D (2025). Lactucin alleviates liver fibrosis by regulating the TLR4-MyD88-MAPK/NF-κB signaling pathway through intestinal flora — animal in vivo. Archives of Biochemistry and Biophysics. https://pubmed.ncbi.nlm.nih.gov/39952453/
9. Zhong Y, Yan J, Lei Y, et al. (2025). Lactucin and lactucopicrin ameliorate obesity in high-fat diet fed mice by promoting white adipose tissue browning through activation of the AMPK/SIRT1/PGC-1α pathway — animal in vivo. Journal of Nutritional Biochemistry. https://pubmed.ncbi.nlm.nih.gov/39909319/
10. Wang X, Liu M, Cai GH, et al. (2020). A potential nutraceutical candidate lactucin inhibits adipogenesis through downregulation of JAK2/STAT3 signaling pathway-mediated mitotic clonal expansion — in vitro. Cells. https://pubmed.ncbi.nlm.nih.gov/32023857/
11. Zheng H, Kang K, Zhang Y, Lin L, Gan L (2025). Lactucin enhances glucose uptake and glycolysis in C2C12 myotubes by activating AMPK signaling pathway — in vitro. Natural Product Research. https://pubmed.ncbi.nlm.nih.gov/41025855/
12. Aibaidula Y, Aimaiti M, Tan H, Chen B, Yang J, Ma X (2022). Lactucin & lactucopicrin ameliorates FFA-induced steatosis in HepG2 cells via modulating lipid metabolism — in vitro. Journal of Pharmacological Sciences. https://pubmed.ncbi.nlm.nih.gov/36055749/
13. Lei Y, Ma XL, Liu T, et al. (2024). Lactucin ameliorates FFA-induced steatosis in HepG2 cells by modulating mitochondrial homeostasis through the SIRT1/PGC-1α signaling axis — in vitro. Heliyon. https://pubmed.ncbi.nlm.nih.gov/39524853/
14. Ma X, Aibaidula Y, Zhang C, et al. (2025). Lactucin alleviates lipid accumulation via AMPK-mediated autophagy and fatty acid β-oxidation in FFA-induced HepG2 cells — in vitro. Journal of Pharmacological Sciences. https://pubmed.ncbi.nlm.nih.gov/40866016/
15. Wei D, Wang PL, Jiang J (2026). Lactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling — animal in vivo (xenograft). Folia Histochemica et Cytobiologica. https://pubmed.ncbi.nlm.nih.gov/42138553/
16. Imam KMSU, Tian Y, Xin F, Xie Y, Wen B (2022). Lactucin, a bitter sesquiterpene from Cichorium intybus, inhibits cancer cell proliferation by downregulating the MAPK and central carbon metabolism pathway — in vitro. Molecules. https://pubmed.ncbi.nlm.nih.gov/36364182/
17. Jang JH, Park CY, Sung EG, et al. (2021). Lactucin induces apoptosis through reactive oxygen species-mediated BCL-2 and CFLAR(L) downregulation in Caki-1 cells — in vitro. Genes & Genomics. https://pubmed.ncbi.nlm.nih.gov/34302634/
18. Bischoff TA, Kelley CJ, Karchesy Y, Laurantos M, Nguyen-Dinh P, Arefi AG (2004). Antimalarial activity of lactucin and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus L. — in vitro. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/15507374/
19. Trojanowska A (2005). Lettuce (Lactuca sp.) as a medicinal plant in Polish publications of the 19th century — historical review. Kwartalnik Historii Nauki i Techniki. https://pubmed.ncbi.nlm.nih.gov/17153150/
20. Ahn Y, Lee HH, Kim BH, et al. (2023). Heukharang lettuce (Lactuca sativa L.) leaf extract displays sleep-promoting effects through GABA-A receptor — animal in vivo. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/37149068/
21. Lee M, Park J, Cho W, et al. (2024). Lactuca sativa L. extract enhances sleep duration through upregulation of adenosine A1 receptor and GABA-A receptor subunits in pentobarbital-injected mice — animal in vivo. Journal of Medicinal Food. https://pubmed.ncbi.nlm.nih.gov/38603571/
22. Kim HD, Hong KB, Noh DO, Suh HJ (2017). Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep — animal in vivo. Food Science and Biotechnology. https://pubmed.ncbi.nlm.nih.gov/30263607/
23. Rollinger JM, Mocka P, Zidorn C, Ellmerer EP, Langer T, Stuppner H (2005). Application of the in combo screening approach for the discovery of non-alkaloid acetylcholinesterase inhibitors from Cichorium intybus — in vitro. Current Drug Discovery Technologies. https://pubmed.ncbi.nlm.nih.gov/16472227/
24. Jaśkiewicz A, Budryn G, Carmena-Bargueño M, Pérez-Sánchez H (2022). Evaluation of activity of sesquiterpene lactones and chicory extracts as acetylcholinesterase inhibitors assayed in calorimetric and docking simulation studies — in vitro. Nutrients. https://pubmed.ncbi.nlm.nih.gov/36079888/
25. Paulsen E, Andersen KE, Hausen BM (2001). Sensitization and cross-reaction patterns in Danish Compositae-allergic patients — clinical study. Contact Dermatitis. https://pubmed.ncbi.nlm.nih.gov/11683829/
26. Paulsen E, Andersen KE (2016). Lettuce contact allergy — review. Contact Dermatitis. https://pubmed.ncbi.nlm.nih.gov/26289653/
27. Paulsen E (2017). Systemic allergic dermatitis caused by sesquiterpene lactones — review. Contact Dermatitis. https://pubmed.ncbi.nlm.nih.gov/27568784/
28. Besharat S, Besharat M, Jabbari A (2009). Wild lettuce (Lactuca virosa) toxicity — case report. BMJ Case Reports. https://pubmed.ncbi.nlm.nih.gov/21686920/
29. Spadari M, Pommier P, Canioni D, Arditti J, David JM, Valli M (2003). Abuse of Lactuca virosa — case report. Presse Médicale. https://pubmed.ncbi.nlm.nih.gov/12762295/
30. Bogdanović M, Cankar K, Dragićević M, et al. (2020). Silencing of germacrene A synthase genes reduces guaianolide oxalate content in Cichorium intybus L. — in vitro. GM Crops & Food. https://pubmed.ncbi.nlm.nih.gov/31668117/
31. Ruggieri F, Hance P, Gioia B, et al. (2023). A three-step process to isolate large quantities of bioactive sesquiterpene lactones from Cichorium intybus L. roots and semisynthesis of chicory STL standards — laboratory method. Pharmaceuticals. https://pubmed.ncbi.nlm.nih.gov/37242554/
32. Schenck G, Loth H, Reubert W (1961). Research on the preparation of lactucin and lactucopicrin from Lactuca virosa plants (15: on the enzymatic and non-enzymatic oxidation of therapeutically active plant substances) — laboratory method. Archiv der Pharmazie. https://pubmed.ncbi.nlm.nih.gov/13747469/
33. Schenck G, Huke M, Naumann T (1964). Studies on the photochemical transformation of lactucin — laboratory study. Archiv der Pharmazie. https://pubmed.ncbi.nlm.nih.gov/5212814/
34. Weng H, He L, Liu X, et al. (2021). Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflamed endothelial cells and improves sepsis in mice — animal in vivo. Biochemical Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33684389/
35. Taechowisan T, Chuen-Im T, Phutdhawong WS (2024). Apoptotic potential and molecular docking of 3,4-dihydro-lactucin, a compound with anticancer properties derived from Microbispora rosea AL22 — in vitro. Anticancer Research. https://pubmed.ncbi.nlm.nih.gov/38423670/
36. Kisiel W, Michalska K (2003). Root constituents of Cichorium pumilum and rearrangements of some lactucin-like guaianolides — in vitro. Zeitschrift für Naturforschung C. https://pubmed.ncbi.nlm.nih.gov/14713151/
37. Michalska K, Szneler E, Kisiel W (2011). Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides — laboratory study. Magnetic Resonance in Chemistry. https://pubmed.ncbi.nlm.nih.gov/22002327/
38. Testone G, Mele G, Di Giacomo E, et al. (2016). Insights into the sesquiterpenoid pathway by metabolic profiling and de novo transcriptome assembly of stem-chicory (Cichorium intybus cultigroup “Catalogna”) — in vitro. Frontiers in Plant Science. https://pubmed.ncbi.nlm.nih.gov/27877190/

View all 38 references▾