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This Paper reviews the most recent advances in synthesizing indole alkaloids using transition metal-catalyzed methods. The essential class of natural substances known as indole alkaloids has several biological effects, including anti-inflammatory, anti-cancer, and anti-bacterial properties. Although there are numerous known natural sources of indole alkaloids, due to their scarcity and complexity, total synthesis has emerged as a promising technique of manufacture. Transition metal-catalyzed methods have become efficient tools for synthesizing indole alkaloids due to their high selectivity and efficiency. The various metal-catalyzed reactions that are used to synthesize indole alkaloids are discussed in this paper, including cross-coupling, cycloaddition, and oxidative cyclization reactions in last five years. [ABSTRACT FROM AUTHOR]

Corydalis yanhusuo W. T. Wang, also known as yanhusuo , yuanhu , yanhu and xuanhu , is one of the herb components of many Chinese Traditional Medicine prescriptions such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was traditionally used to relieve pain and motivate blood and Qi circulation. Now there has been growing interest in pharmacological effects of alkaloids, the main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. yanhusuo are its important bioactive components and can be characterized into protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and proper extraction or co-administration methods modulate their contents and efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the nervous system, cardiovascular system, cancer and others through multiple molecular mechanisms such as modulating neurotransmitters, ion channels, gut microbiota, HPA axis and signaling pathways and are potential treatments for many diseases. Plenty of novel drug delivery methods such as autologous red blood cells, self-microemulsifying drug delivery systems, nanoparticles and others have also been investigated to better exert the effects of alkaloids from C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo , their pharmacological effects and mechanisms, and methods of drug delivery to lay a foundation for future investigations. [Display omitted] • This paper summarized 84 alkaloids from C. yanhusuo. • This paper reviewed pharmacological effects of alkaloids from C. yanhusuo. • This paper summed up mechanisms of alkaloids from C. yanhusuo against diseases. • This paper reviewed drug delivery methods of alkaloids from C. yanhusuo. [ABSTRACT FROM AUTHOR]

Pepper sprays of the OC type constitute the majority of self-defense sprays available on the market. The active ingredient in these preparations is pepper extract: Oleoresin Capsicum, which contains capsaicinoids - natural compounds with irritant properties. Preparations from OC pepper sprays can be distinguished based on differences in the quantitative ratios of four main capsaicinoids: capsaicin, dihydrocapsaicin, nordihydrocapsaicin, and nonivamide. This raises the question whether information on the quantitative ratios of capsaicinoids can also provide answers to questions regarding comparisons of traces of OC preparations, such as whether traces revealed on the clothing of the victim could originate from an OC spray secured from the suspect, or whether traces on the clothing of the suspect and the victim could come from the same pepper spray. Such comparisons would be viable only if the capsaicinoid profile remained unchanged during evidence storage and as a result of solvent extraction from the tested material. The aim of the presented research was to determine if this is indeed the case. Model aging experiments were conducted to examine whether the capsaicinoid profile in traces of OC preparations changed over time and whether solvent extraction affected this profile. Samples of five different OC preparations were applied to cotton swabs, which, after the evaporation of volatile solvents, were placed in three types of packaging with varying levels of tightness and transparency (tight amber vials, polyethylene bags, paper envelopes). These prepared samples underwent solvent extraction with methanol and analysis using gas chromatography – mass spectrometry, after 28, 84, 147, 196, 252, and 301 days from preparation. The likelihood ratio (LR) was applied as a statistical tool to investigate the data obtained. The LR model was computed using the three variables based on the relative content of nordihydrocapsaicin, nonivamide, and dihydrocapsaicin. The cotton swabs used in the experiments served as a model for both the swabs used by the police for securing liquid evidence and the cotton clothing of individuals sprayed with OC pepper sprays. The findings of the conducted studies suggest that the quantitative relationships of capsaicinoids indeed change over time, both in preparations stored in original containers and in traces of these preparations present on clothing. For traces of OC preparations secured on swabs or present on clothing, these changes are more significant the longer the sample is stored and the less airtight the packaging used. [Display omitted] • Pepper sprays differ in the quantitative ratios of capsaicinoids. • The capsaicinoid profile in traces, e.g., on clothing, changes over time. • Changes depend on the storage duration and packaging method of the samples. • Changes are more significant with longer storage time and less airtight packaging. • Comparing capsaicinoid profiles in traces and preparations is not advisable. [ABSTRACT FROM AUTHOR]

Ionic Liquid based micellar structures were probed using spectroscopy and microscopy analysis. [Display omitted] • Switching between neutral and cation forms of SANG is used to probe IL based premicellar and micellar structures. • [Bmim][Os] IL micelles converted SANG from iminium form to alkanolamine. • Concentration dependent morphologies of IL self-assemblies were characterized by AFM and other spectroscopic tools. • Time-resolved properties of alkanolamine showed accurate transition points for premicellar and micellar structures. In this paper, we report the structural and dynamics aspect of self-assembled nano structures formed by an ionic liquid (IL) based surfactant, 1-butyl-3-methylimidazolium [Bmim] octyl sulfate [Os] using photophysical properties of a well-known anti-cancer alkaloid, sanguinarine (SANG). SANG exists in two forms, iminium and alkanolamine, in aqueous solutions at equilibrium which gets disturbed upon addition of [Bmim][Os] IL. The anionic part of this IL is micellar in nature and induces the iminium form to convert into alkanolamine form after reaching critical micelle concentration (CMC) at 31–34 mM. The gradual conversion from iminium to alkanolamine with [Bmim][Os] exhibits interesting transition points at various concentrations of IL. Importantly, on adding IL, the increment in alkanolamine emission at 415 nm exhibited a different trend when compared with iminium emission at 565 nm. Only one transition point at CMC was seen by alkanolamine emission intensity whereas iminium fluorescence undergoes three different slopes of quenching. Atomic force microscopy (AFM) detected different morphologies at 10, 20 and 35 mM concentrations of [Bmim][Os]. Interestingly, time-resolved properties of alkanolamine showed an efficient way for detecting these premicellar transitions. Along with the alkanolamine lifetime component inside the micelle (2.9 ns), the appearance of a short component of fluorescence lifetime ∼ 1.6 ns was characterized as SANG-sulfate interactions using the [Bmim][HSO 4 ]. Overall, three regions of premicellar and micellar states were observed based on spectroscopic analysis of iminium and alkanolamine forms. This kind of switching between prototropic forms of the drug by a surface-active IL (SAIL) is an important aspect for alkaloids and can find potential applications in drug loading and delivery methods. [ABSTRACT FROM AUTHOR]

• Emetine and dehydroemetine inhibit both coronavirus growth and host-cell protein synthesis at nanomolar concentrations. • The stereochemical requirements of emetine and its analogs for inhibition of both viral growth and host-cell protein synthesis inhibition are the same. • Cardiotoxic effects of emetine and dehydroemetine at I CaL are not stereo-specific and require micromolar concentrations. The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC 50 ∼ 50–100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC 50 ∼ 40–60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation. [ABSTRACT FROM AUTHOR]

• Effect of age and location on various narcissus alkaloids is quantified in this paper. • Results clearly indicate that age have a significant effect on different alkaloid contents specifically galanthamine. • It is also evident that effect of location on galanthamine contents is not significant but contents of other alkaloids vary significantly due to location. Narcissus is mostly grown for horticultural/decorative purposes in the fields and home gardens. Previously, galanthamine isolation (from the bulbs to produce medicine for the treatment of Alzheimer's disease) has been established as a novel use. Moreover, recent studies have also shown that Narcissus bulbs are also a source of several other interesting biologically active compounds and particularly some alkaloids. Various metabolites are produced at different time points during the growth cycle of plants. Also, for Narcissus bulbs it is important to find from an economical point of view the optimum time point for harvesting in its growth cycle, as the levels of galanthamine might be correlated with the age of the Narcissus bulbs. The aim of this study was to investigate the differences in the metabolites and specifically in the alkaloid contents based on a 1, 2- or 3-years harvesting cycle of Narcissus bulbs. Moreover, the effect of the cultivation site was studied for Narcissus pseudonarcissus cv Carlton which is well known for galanthamine production. Different methods were used for the analysis of these alkaloids. Untargeted NMR based metabolomics was used for overall metabolic changes and galanthamine quantitation. Whereas targeted GC-FID and GC–MS were used respectively for quantitative and qualitative analysis of major and minor alkaloids. An alkaloid specific acid-base extraction method was used in the GC–MS and GC–FID analysis. The results show that the contents of the metabolites vary significantly with the age of the bulbs. The contents of galanthamine were highest in two years old bulbs. It was also found that the alkaloid contents from the same variety grown at different locations differ from each other. Results presented here clearly indicate that] age of the bulb are important factors to consider for the industrial production of certain alkaloids from the plants as yields of alkaloids may vary, certain conditions may lead to an increase of the yield with 10–15%. [ABSTRACT FROM AUTHOR]

Abstract Piperine (E,E-) is a naturally occurring pungent and spicy constituent of black pepperand is also used as an added flavoring ingredient to foods and beverages. Piperine has been determined safe under conditions of intended use as a flavoring substance by regulatory and scientific expert bodies. While concurring with the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and Flavor and Extract Manufacturers Association (FEMA) Expert Panel on the safety of piperine, the European Food Safety Authority (EFSA) requested additional toxicological data. The results of a 90-day GLPcompliant dietary study, conducted in Sprague-Dawley rats at target doses of 0, 5, 15, or 50 mg/kg bw/day, to respond to this request are presented herein. No adverse effects were found attributable to ingestion of piperine. Statistically significant changes in food consumption, body weight gain, and plasma cholesterol levels were not considered adverse as discussed in this paper. Therefore, the oral no-observed-adverse-effect level (NOAEL) was determined to be the highest dose tested of 50 mg/kg bw/day. EFSA derived a lower NOAEL of 5 mg/kg bw/day based on increased plasma cholesterol levels which still affords an adequate margin of safety of over 48,000 and concluded that piperine is not of safety concern. Highlights • GLP-compliant 90-day study of piperine following OECD guideline. • Piperine produces no adverse effects in rats fed diets containing up to 3600 ppm of added flavor for 90 days. • A threshold of toxicity (NOAEL) of 50 mg/kg bw/day is proposed for piperine. [ABSTRACT FROM AUTHOR]

Abstract: This introduction to the journal’s supplement on probabilistic risk assessment of single and multiple exposure to pesticide residues or contaminants summarizes the objectives and results of the work performed in work package 3 of the EU-funded project SAFE FOODS. Within this work package, we developed an electronic platform of food consumption and chemical concentration databases harmonised at raw agricultural commodity level. In this platform the databases are connected to probabilistic software to allow probabilistic modelling of dietary exposure in a standardised way. The usefulness of this platform is demonstrated in two papers, which describe the exposure to pesticides and glycoalkaloids in several European countries. Furthermore, an integrated probabilistic risk assessment (IPRA) model was developed: a new tool to integrate exposure and effect modelling, including uncertainty analyses. The use of this model was shown in a paper on the cumulative exposure to anti-androgen pesticides. Combined with a health impact prioritization system, developed within this work package to compare heath risks between chemicals, the IPRA tool can also be used to compare health risks between multiple chemicals in complex risk assessment situation such as risk–benefit and risk trade-off analyses. Both the electronic platform of databases as the IPRA model may proof to be powerful tools to tackle the challenges risk managers are or will be faced with in the future. [Copyright &y& Elsevier]

The considerable amounts of alkaloids in tobacco stem (TS) make it wasteful and environmentally detrimental to directly pyrolyze it. This paper reveals the effects of leaching treatments with different solvents (hydrochloric acid, water and ethyl alcohol) on the pyrolysis characteristics of TS using TG-FTIR and Py-GC–MS. Alkaloids mainly consisting of nicotine were almost completely removed by leaching treatments, leading to the reduction of the N content in treated samples and the reduction of N-containing compounds in the obtained tar by Py-GC–MS. Potassium and calcium, which are the two main cations in TS, were removed completely by acid leaching, whereas calcium is resistant to water and alcohol. The removal of inorganic species in leached samples reduced the stability of TS at low temperatures (<∼270 °C) but improved it at high temperatures (270–490 °C). In addition, more sugars, such as levoglucosan, and high-mass weight species were generated by pyrolysis of TS leached by several solvents, especially acid. Different from water and alcohol, hydrochloric acid strongly destroyed the matrix structure of TS and lowered its thermal stability. Because of the removal of acid-soluble lignin by hydrochloric acid, the generation of benzenes during pyrolysis were markedly inhibited. [ABSTRACT FROM AUTHOR]

It is reported in this study the effect of isolates from leaves of Aristotelia chilensis as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes. The aim of the paper was to evaluate the activity of A. chilensis towards different enzymes. In addition to pure compounds, extracts rich in alkaloids and phenolics were tested. The most active F5 inhibited AChE (79.5% and 89.8% at 10.0 and 20.0 μg/mL) and against BChE (89.5% and 97.8% at 10.0 and 20.0 μg/mL), showing a strong mixed-type inhibition against AChE and BChE. F3 (a mixture of flavonoids and phenolics acids), showed IC 50 of 90.7 and 59.6 μg/mL of inhibitory activity against AChE and BChE, inhibiting the acetylcholinesterase competitively. Additionally, F3 showed and high potency as tyrosinase inhibitor with IC 50 at 8.4 μg/mL. Sample F4 (anthocyanidins and phenolic composition) presented a complex, mixed-type inhibition of tyrosinase with a IC 50 of 39.8 μg/mL. The findings in this investigation show that this natural resource has a strong potential for future research in the search of new phytotherapeutic treatments for cholinergic deterioration ailments avoiding the side effects of synthetic drugs. This is the first report as cholinesterases and tyrosinase inhibitors of alkaloids and phenolics from A. chilensis leaves. [ABSTRACT FROM AUTHOR]

Illigera henryi , an endemic traditional Chinese medicine, contains abundant aporphine alkaloids that possess various bioactivities. In the present study, tubers of I. henryi were fermented by several fungi, and the acetylcholinesterase (AChE) inhibitory activities of non-fermented and fermented I. henryi were measured. The results showed that the fermentation of I. henryi with Clonostachys rogersoniana 828H2 is effective for improving the AChE inhibitory activity. A key biotransformation was found during the C. rogersoniana fermentation for clarifying the improvement of the AChE inhibitory activity of I. henryi : ( S )-actinodaphnine ( 1 ) was converted to a new 4-hydroxyaporphine alkaloid (4 R ,6a S )-4-hydroxyactinodaphnine ( 2 ) that possessed a stronger AChE inhibitory activity, with an IC 50 value of 17.66 ± 0.06 μM. This paper is the first to report that the pure strain fermentation processing of I. henryi and indicated C. rogersoniana fermentation might be a potential processing method for I. henryi . [ABSTRACT FROM AUTHOR]

Opium is a substance extracted from Papaver somniferum L. Opium latex contains morphine, codeine, and thebaine and non-analgesic alkaloids such as papaverine and noscapine. In Spain opium growing is allowed only for scientific or pharmaceutical purposes and harvest is supervised by the Spanish Health Ministry. This work describes a sudden fatality involving opium consumption in a legal poppy field. The toxicological and autopsy findings, previous disease, paraphernalia, and scenario are discussed in order to clarify cause and manner of death. A 32-year-old white caucasian male was found unresponsive in a legal poppy field in the South of Spain. The emergency medical services responded to the scene where he was pronounced dead. The friends explained that the deceased had presented with about 30min of convulsions; in spite of trying to keep his airway tract open they noted that "he stayed airless". According to them the victim suffered from epilepsy. Tools found beside his body consisted of plain wood sticks with a blade razor, a fabric handle, and paper. A comprehensive toxicological screening for abuse and psychoactive drugs was performed in the deceased samples. This included ethanol and volatile analysis by HS-GC-FID in peripheral blood and urine, enzyme immunoassay in urine by CEDIA, and a basic drug screening in all samples (including paraphernalia) by GC-MS using modes full scan for screening/confirmation and selected ion monitoring for quantitation. The peripheral blood, urine, vitreous, and gastric content contained the following concentrations of opiates expressed in mg/L (gastric content additionally also expressed in mg total): 0.10, 7.12, 0.23, and 14.80 (2.81mg total) of thebaine, 0.13, 4.50, 0.13, and 6.60 (1.25mg total) of morphine (free), 0.48, 0.88, 0.17, and 1.50 (0.28mg total) of codeine. These tree opiates were also detected in the tools (paraphernalia) used by the deceased for opium consumption. Other toxicological findings were metabolites of cocaine and cannabis. Apparently the victim stole poppy capsules and ingested an unknown quantity of the latex with the goal to obtain euphoric effects. The cause of death was considered poly-drug toxicity with a preponderant role of thebaine and morphine. In addition, the epileptic condition of the deceased could have played a role. As far as we know, there are no previous reports of fatalities occurring in legal poppy fields. [ABSTRACT FROM AUTHOR]

Background: Dendrobium Sw. has been used for thousands of years in China as a precious traditional Chinese medicine. It is derived from stems of various Dendrobium plants and has the functions of nourishing Yin and clearing heat, activating water and nourishing the stomach, moistening the lung and relieving cough. Modern phytochemical studies show that the main components of Dendrobium include alkaloids, polysaccharides, terpenoids, diphenylbenzene, and phenanthrene. Alkaloids are natural products with obvious biological activity and are important effective components of the medicinal activity or toxicity of plants. At present, dozens of alkaloids with various structures have been isolated from Dendrobium plants, and the alkaloid contents in Dendrobium plants of different species are quite different. From the perspective of food safety, the type, molecular structure, content and potential physiological activity or toxicity of alkaloids are important bases for evaluating the safety of edible plants. Studies have shown that the alkaloids isolated from Dendrobium have neuroprotective, anti-inflammatory and antitumor activities, showing that these alkaloids with potential medicinal activity are important sources of lead compounds in innovative drug development.Purpose: To summarize the research progress on alkaloids in Dendrobium and provide a reference for research on the food safety and medicinal development of Dendrobium.Method: Information about alkaloids from Dendrobium was collected from the scientific databases Web of Science, PubChem and PubMed. We discuss the biosynthetic pathway, biological activities and total synthesis of alkaloids from Dendrobium from 1964 to 2020 and summarize the knowledge of alkaloids from Dendrobium, the biosynthetic pathway, biological activities and total synthesis. We chose publications on their chemistry, drug effects, pharmacology, metabolism and biosynthesis, physiology and toxicity. Alkaloids, Dendrobium, biosynthetic pathway and biological activities were used as keywords to extract the relevant literature.Conclusion: In this paper, the structural classification, biological activity, target and toxicology and synthesis of the alkaloids in Dendrobium were systematically reviewed, which will provide a reference for the safety, development and application of Dendrobium. [ABSTRACT FROM AUTHOR]

The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents. [Display omitted] • Several natural products are reported highly effective in COVID-19 therapy. • Therapeutic potential, biochemical properties and mechanism of action of essential phytoconstituents are discussed. • The mechanism of action of a few effective phytoconstituents in COVID-19 therapy are highlighted. • These phytoconstituents represent a promising option for targeting SARS-CoV-2 pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Aim: A drug and alcohol withdrawal rehabilitation centre requested an analysis for “Krypton” in urine of a former opiate-addictive woman. She showed an altered clinical picture and behaviour with miosis, itchiness, agitation, and moderate euphoria after 3 months of until than successful treatment. Literature search revealed that “Krypton” is said to contain “Kratom” (leaves of Mitragyna speciosa), but could also contain O-desmethyltramadol (European Monitoring Centre for Drugs and Drug Addiction thematic paper “Spice”). Methods: Immunological drug screenings were done with test strips (nal von minden, Regensburg, Germany) and with cloned enzyme donor immunoassay (Microgenics, Passau, Germany). “Kratom” alkaloids and tramadol (metabolites) were analyzed by LC–MS/MS (ThermoFisher Scientific Quantum Ultra Triple Quadrupole mass spectrometer). Results: Immunoassays were negative for amphetamines, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, ethylglucuronide, methadone (metabolite), opiates, oxycodone, and THC-COOH, and test strips were negative for tramadol and its metabolites (cut-off 10mg/L for O-desmethyltramadol). LC–MS/MS detected the “Kratom” alkaloids mitragynine, speciociliatine, speciogynine, mitraciliatine, and paynantheine and approximately 9mg/L O-desmethyltramadol, but no tramadol and N-desmethyltramadol. Discussion: The detection of M. speciosa alkaloids is a proof of “Kratom” abuse. Confronted with the analysis data, the patient admitted to have consumed 3–4 infusions of “Krypton”. The origin of the O-desmethyltramadol is unclear. Tramadol abuse is unlikely since tramadol and N-desmethyltramadol (physiologically occurring in urine after tramadol intake) were not detectable. Consumption of a “Krypton” product spiked with O-desmethyltramadol could explain our findings and the patient''s clinical picture. This would be in agreement with a most recent report about spiking apparently natural herbal mixtures with the synthetic opioid O-desmethyltramadol. Conclusion: Analysis of “Kratom” abuse should not be restricted to M. speciosa alkaloids, but should also consider synthetic drugs which could be added to the herbal mixtures. Mass spectrometry based drug screenings will gain importance to keep pace with the dynamic drug market. [Copyright &y& Elsevier]

Abstract: In this paper, we present an approach to format national food consumption data at raw agricultural commodity (RAC) level. In this way, the data is both formatted in a harmonised way given the comparability of RACs between countries, and suitable to assess the dietary exposure to chemicals analysed in RACs at a European level. In this approach, consumption data needs to be converted to edible part of RAC (e-RAC) level using a RAC conversion database. To subsequently use this data in exposure assessments, both e-RACs and RACs analysed in chemical control programmes should be classified via a uniform system. Furthermore, chemical concentrations in RACs may need to be converted to e-RAC level using processing factors. To illustrate the use of this approach, we describe how the Dutch RAC conversion database was used to convert consumption data of four national consumption surveys to e-RAC level, and the use of the FAO/WHO Codex Classification system of Foods and Animal Feeds to harmonise the classification. We demonstrate that this approach works well for pesticides and glycoalkaloids, and is an essential step forward in the harmonisation of risk assessment procedures within Europe when addressing chemicals analysed in RACs by all national food control systems. [Copyright &y& Elsevier]

Abstract: Many plants contain toxic alkaloids which may be dangerous to humans. Despite the large number of poisonous plants, cases of fatal plant poisonings are relatively rare. The frequencies of poisonings and the plants involved are often regionally specific. Plant poisonings can be aggregated into three categories: unintended ingestions, intended ingestions, and poisoning due to abuse of plant material. Unintended ingestions often occur in children or from a mix-up of plants and mushrooms in adults. Intended ingestions are common in homicides and suicides. Increasingly common is the abuse of plants for hallucinogenic reasons. Toxicological analysis of such alkaloids may help in diagnosis of poisoning or abuse cases. This review describes the toxic alkaloids aconitine, atropine, coniine, colchicine, cytisine, dimethyltryptamine, harmine, harmaline, ibogaine, kawain, mescaline, scopolamine, and taxine, which are often involved in fatal and non-fatal poisonings. The paper summarizes the symptoms of the intoxications and reviews the methods of detection of their toxic constituents in biological fluids. [Copyright &y& Elsevier]

Abstract: To study the cytotoxicity of four alkaloids: brucine, strychnine, brucine N-oxide and isostrychnine from nux vomica on SMMC 7721 cells and their possible mechanisms, MET assay was used to examine the growth inhibitory effects of these alkaloids. Brucine revealed the strongest growth inhibitory effect on SMMC-7721 cells. Furthermore, as directly observed under an inverted microscope, fluorescent microscope and transmission electronic microscope, brucine caused SMMC-7721 cell shrinkage, membrane blobbing, formation of apoptotic body as well as nucleus condensation, all of which are typical characteristics of apoptotic programmed cell death. In addition, brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase 3 as well as cyclooxygenase 2 inhibition, since neither caspase 3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E2 able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis. In sum, this paper indicate that the major alkaloids present in the seed of Strychnos nux-vomica are effective against SMMC-7721 cells proliferation, among which brucine proceeds SMMC-7721 cells death via apoptosis, probably through the participation of caspase 3 and cyclooxygenase 2. [Copyright &y& Elsevier]

Sanguinaria canadesis, Chelidonium majus and Macleya cordata have been used for centuries as alternative medicines. Currently the extracts from these medicinal plants are components of veterinary and human phytopreparations, and of oral-hygiene agents. Sanguinarine and chelerythrine (SA/CHE) are biologically active components of these extracts. They display distinct antibacterial and anti-inflammatory properties, but, on the other hand, they have been reported as having adverse effects — genotoxicity and hepatotoxicity. This paper is aimed at evaluation of the effects of daily administration of the extract from Macleya cordata (2 mg and 100 mg in 1 kg feed, sanguinarine:chelerythrine 3:1) in the diet on the health status of swine. After 90-day administration, alkaloids were retained to a different extent in tissues. The highest SA/CHE retention was detected in the gingiva (0.55 μg/g) and liver (0.15 μg/g), no SA/CHE were detected in muscles. Plasma SA levels attained 0.11 μg/ml. Treated animals did not display any results of hematological, biochemical or histological assay different from controls. A 32P-postlabeling assay proved that no DNA-adducts with SA/CHE were detected in pig livers. We did not observe any symptom linked to epidemic dropsy syndrome often attributed to sanguinarine. In conclusion, an average daily oral dose of alkaloids up to 5 mg per 1 kg animal body weight proved to be safe. [Copyright &y& Elsevier]

Abstract: This paper presents seven fatal cases of aconite poisoning encountered in the Tongji Center for Medicolegal Expertise in Hubei (TCMEH), China, from 1999 to 2008 retrospectively. In six of the cases, deaths occurred after drinking homemade medicated liquor containing aconite, and in one case death was due to ingestion of traditional Chinese medication containing aconite. Forensic autopsy and pathological examinations ruled out the presence of physical trauma or life-threatening diseases. Diagnosis of aconite poisoning was made after postmortem toxicological analysis. Animal experiment was performed in one case demonstrating that the medicated liquor could cause death rapidly. We present the autopsy and histopathological findings, toxicological analysis, and results of animal experiment done on samples from those seven cases. As an important herbal Chinese medicine, Aconitum species deserve special attention, especially because it contains poisonous alkaloids. [Copyright &y& Elsevier]