Death of Socrates: a likely case of poison hemlock (Conium maculatum) poisoning.

INTRODUCTION: The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others. THE EVIDENCE: Socrates' death has almost always been attributed to his drinking an extract of poison hemlock, Conium maculatum, despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains. EVALUATION: Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato. CONCLUSIONS: Seen in this way, the death of Socrates can be accepted as a limited case report of Conium maculatum poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.

Evaluation of therapeutic and toxic levels of Conium maculatum L. extract in gestation and foetal development of adult albino rats.

BACKGROUND: Conium maculatum L. (C.M) is a poisonous plant species particularly for animals including mainly cattle. Even though it is known for its toxicity, clinically has significance due to sedative, antispasmodic and anti-inflammatory properties. For the first time present this study designed to investigate the therapeutic and fatal doses of C.M extract in gestated albino Wistar rats. OBJECTIVE: To evaluate the therapeutic and toxic levels of different concentrations of C.M extract in gestation and foetal development of adult albino Wistar rats. MATERIALS AND METHODS: C.M extract at different doses of 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg and 50 mg/kg was orally administered to rats in the entire gestation period. The changes in morphology of mother and siblings, foetal formation, pups birth rate, pups survival rate and AchE levels, MAO levels, and Dopamine levels were measured to ensure the nonlethal dose of the extract. RESULTS: In the treated mother rat group, 50 mg/kg concentration caused death and 20 mg/kg concentration of extract showed good therapeutic values. Birth rate, survival rate, dopamine, MAO levels, SOD, AchE and protein levels decreased upon increasing concentration, whereas LPO and MAO levels increased in mother and sibling rats. Histopathological studies showed that 20 mg/kg concentration of extract showed no damage in neuron cells with maximum increase in number. CONCLUSION: Our findings suggests that C.M 50 mg/kg dose is a toxic concentration in the mother group whereas 40 mg/kg dose in sibling rats by increasing the levels free radicals, decreasing AchE neurotransmitters level, and increasing MAO levels.

What Socrates drank? Comparative chemical investigation of two Greek Conium taxa exhibiting diverse chemical profiles.

Conium divaricatum, even though exhibiting morphological differences in comparison to its congener of European origin Conium maculatum, is still considered a disputed taxon often referred to as a synonym of the latter. Herein, essential oils of various plant tissues from several populations of both taxa were comparatively investigated, showing distinct chemical profiles. In the case of C. divaricatum, the essential oils were dominated by hydrocarbon esters, among which the main constituents 4'-oxodecyl hexanoate, 4'-oxododecyl hexanoate and 4'-oxooctyl hexanoate were isolated and identified as undescribed natural products. In contrast, the essential oils of C. maculatum were dominated by hydrocarbon alkanes, alkenes and ketones, as well as the polyacetylene (Z)-falcarinol. Even though determination of the total alkaloids content and toxicity assessment against the crustacean Artemia salina did not reveal significant differences, the distinct chemical profiles and the morphological differences observed for both taxa, strongly support their distinction as separate species.

Characterization of Phytoconstituents from Alcoholic Extracts of Four Woody Species and Their Potential Uses for Management of Six Fusarium oxysporum Isolates Identified from Some Plant Hosts.

BACKGROUND: Trees are good sources of bioactive compounds as antifungal and antioxidant activities. METHODS: Management of six molecularly identified Fusarium oxysporum isolates (F. oxy 1, F. oxy 2, F. oxy 3, F. oxy 4, F. oxy 5 and F. oxy 6, under the accession numbers MW854648, MW854649, MW854650, MW854651, and MW854652, respectively) was assayed using four extracts from Conium maculatum leaves, Acacia saligna bark, Schinus terebinthifolius wood and Ficus eriobotryoides leaves. All the extracts were analyzed using HPLC-VWD for phenolic and flavonoid compounds and the antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and ß-carotene-linoleic acid (BCB) bleaching assays. RESULTS: In mg/kg extract, the highest amounts of polyphenolic compounds p-hydroxy benzoic, benzoic, gallic, and rosmarinic acids, with 444.37, 342.16, 311.32 and 117.87, respectively, were observed in C. maculatum leaf extract; gallic and benzoic acids with 2551.02, 1580.32, respectively, in A. saligna bark extract; quinol, naringenin, rutin, catechol, and benzoic acid with 2530.22, 1224.904, 798.29, 732.28, and 697.73, respectively, in S. terebinthifolius wood extract; and rutin, o-coumaric acid, p-hydroxy benzoic acid, resveratrol, and rosmarinic acid with 9168.03, 2016.93, 1009.20, 1156.99, and 574.907, respectively, in F. eriobotryoides leaf extract. At the extract concentration of 1250 mg/L, the antifungal activity against the growth of F. oxysporum strains showed that A. saligna bark followed by C. maculatum leaf extracts had the highest inhibition percentage of fungal growth (IPFG%) against F. oxy 1 with 80% and 79.5%, F. oxy 2 with 86.44% and 78.9%, F. oxy 3 with 86.4% and 84.2%, F. oxy 4 with 84.2, and 82.1%, F. oxy 5 with 88.4% and 86.9%, and F. oxy 6 with 88.9, and 87.1%, respectively. For the antioxidant activity, ethanolic extract from C. maculatum leaves showed the lowest concentration that inhibited 50% of DPPH free radical (3.4 µg/mL). Additionally, the same extract observed the lowest concentration (4.5 µg/mL) that inhibited BCB bleaching. CONCLUSIONS: Extracts from A. saligna bark and C. maculatum leaves are considered potential candidates against the growth of F. oxysporum isolates-a wilt pathogen-and C. maculatum leaf as a potent antioxidant agent.

Mild-to-severe poisoning due to Conium maculatum as toxic herb: A case series.

Conium maculatum toxicity may occur by mistakenly or intentionally eating this plant. Due to muscarinic or nicotinic symptoms associated with this plant toxicity, supportive care and treatment with atropine are urgently important.

Diversity of Secondary Metabolites in Roots from Conium maculatum L.

BACKGROUND: Conium maculatum is known as highly toxic plant, due to piperidine alkaloids present in the aerial parts. In a first attempt, in various tap root samples, however, alkaloids could not be detected. The present study describes active compounds in the tap roots from 16 populations harvested at maturity. The compounds were extracted with dichloromethane from root pieces of single plants and analyzed by gas chromatography-mass spectrometry. Ten bioactive compounds were evaluated: five furocoumarins, two prenylated coumarins, two aliphatic C17-polyacetylenes and the phenylpropanoid elemicin. A high variability could be observed, the highest concentrations were measured for falcarindiol, xanthotoxin and isopimpinellin, the lowest for elemicin. In sum C. maculatum roots contained comparable amounts of compounds that are characteristic for Apiaceae, and also occur in vegetables as carrots, parsnip, parsley or celeriac.

The killer of Socrates: Coniine and Related Alkaloids in the Plant Kingdom.

Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine's most famous victim is Socrates who was sentenced to death by poison chalice containing poison hemlock in 399 BC. In chemistry, coniine holds two historical records: It is the first alkaloid the chemical structure of which was established (in 1881), and that was chemically synthesized (in 1886). In plants, coniine and twelve closely related alkaloids are known from poison hemlock (Conium maculatum L.), and several Sarracenia and Aloe species. Recent work confirmed its biosynthetic polyketide origin. Biosynthesis commences by carbon backbone formation from butyryl-CoA and two malonyl-CoA building blocks catalyzed by polyketide synthase. A transamination reaction incorporates nitrogen from l-alanine and non-enzymatic cyclization leads to γ-coniceine, the first hemlock alkaloid in the pathway. Ultimately, reduction of γ-coniceine to coniine is facilitated by NADPH-dependent γ-coniceine reductase. Although coniine is notorious for its toxicity, there is no consensus on its ecological roles, especially in the carnivorous pitcher plants where it occurs. Lately there has been renewed interest in coniine's medical uses particularly for pain relief without an addictive side effect.

Polyketide synthases from poison hemlock (Conium maculatum L.).

Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl-CoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full-length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs.

Anticancer potential of Conium maculatum extract against cancer cells in vitro: Drug-DNA interaction and its ability to induce apoptosis through ROS generation.

OBJECTIVE: Conium maculatum extract is used as a traditional medicine for cervix carcinoma including homeopathy. However, no systematic work has so far been carried out to test its anti-cancer potential against cervix cancer cells in vitro. Thus, in this study, we investigated whether ethanolic extract of conium is capable of inducing cytotoxicity in different normal and cancer cell lines including an elaborate study in HeLa cells. MATERIALS AND METHODS: Conium's effects on cell cycle, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) and apoptosis, if any, were analyzed through flow cytometry. Whether Conium could damage DNA and induce morphological changes were also determined microscopically. Expression of different proteins related to cell death and survival was critically studied by western blotting and ELISA methods. If Conium could interact directly with DNA was also determined by circular dichroism (CD) spectroscopy. RESULTS: Conium treatment reduced cell viability and colony formation at 48 h and inhibited cell proliferation, arresting cell cycle at sub-G stage. Conium treatment lead to increased generation of reactive oxygen species (ROS) at 24 h, increase in MMP depolarization, morphological changes and DNA damage in HeLa cells along with externalization of phosphatidyl serine at 48 hours. While cytochrome c release and caspase-3 activation led HeLa cells toward apoptosis, down-regulation of Akt and NFkB inhibited cellular proliferation, indicating the signaling pathway to be mediated via the mitochondria-mediated caspase-3-dependent pathway. CD-spectroscopy revealed that Conium interacted with DNA molecule. CONCLUSION: Overall results validate anti-cancer potential of Conium and provide support for its use in traditional systems of medicine.

Hemlock (Conium Maculatum) Poisoning In A Child.

Poison hemlock (Conium maculatum) is a plant that is poisonous for humans and animals. Accidental ingestion of the plant may result in central nervous system depression, respiratory failure, acute rhabdomyolysis, acute renal failure and even death. The main treatment of hemlock poisoning is supportive care. The case of a 6-year-old girl who was admitted to the emergency department with complaints of burning sensation in mouth, hypersalivation, tremor in hands and ataxia after ingestion of poison hemlock is presented here with clinical and laboratory features. In this case, we aim to report that accidental ingestion of plants resembling vegetables that are consumed daily can lead to serious complications and even death.

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity.

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1(st) h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum.