Gelsemium elegans Benth: Chemical Components, Pharmacological Effects, and Toxicity Mechanisms.

Gelsemium elegans Benth (GEB), also known as heartbreak grass, is a highly poisonous plant belonging to the family Loganiaceae and genus Gelsemium that has broad application prospects in medicine. This article reviews its chemical components, pharmacological effects, toxicity mechanisms, and research progress in clinical applications in recent years. Indole alkaloids are the main active components of GEB and have a variety of pharmacological and biological functions. They have anti-tumor, anti-inflammatory, analgesic, and immunomodulation properties, with the therapeutic dose being close to the toxic dose. Application of small-dose indole alkaloids fails to work effectively, while high-dose usage is prone to poisoning, aggravating the patient's conditions. Special caution is needed, especially to observe the changes in the disease condition of the patients in clinical practice. In-depth research on the chemical components and mechanisms of GEB is essential to the development of promising lead compounds and lays the foundation for extensive clinical application and safe usage of GEB in the future.

Gravimetric quantitative validation of botanic impurities in feed.

BACKGROUND: Harmful botanical impurities may contaminate feed and feed materials and be a potential danger to animal or human health, or to the environment. The aim of this study was to establish rapid and sensitive methods that can be used in routine official controls to determine botanical impurities such as Datura stramonium, Ricinus communis, Crotaliaria spp., and Ambrosia spp. in animal feed and raw materials. Claviceps sclerotia were also detected in cereals, due to the similarities of the targets and the analytical procedure. Regulation (EU) 625/2017, which replaces Reg. 2004/882/EC, states that EU member states should conduct official controls in assessed and accredited laboratories and that the analytical methods must be validated before use by considering parameters such as specificity, precision, recovery, and measurement uncertainly. RESULTS AND CONCLUSION: The results demonstrate that all of the methods tested are suitable for the official quantitative analyses required by EU official legislation. © 2020 Society of Chemical Industry.

Palicourea marcgravii (Rubiaceae) poisoning in cattle grazing in Brazil.

Palicourea marcgravii is the most important poisonous plant of cattle in Brazil. It contains monofluoroacetic acid and causes sudden death associated with exercise. Herein, we describe the temporal and spatial distribution of the toxic disease. The survey was based on the epidemiological, clinical, and pathological data of the Setor de Anatomia Patológica (SAP) of the Universidade Federal Rural do Rio de Janeiro (UFRuralRJ) to report outbreaks of poisoning by P. marcgravii, from 1953 to 2018. Clinical signs were peracute and included labored breathing, loss of balance, muscle tremors, lateral recumbency, and limb paddling. Gross lesions such as congestion of large vessels and edema and pulmonary congestion were observed. Multifocal areas of vacuolar hydropic degeneration of distal contorted tubule cells with nuclear pyknosis were observed in the kidneys. The plant is found in forests, and the poisoning occurs mainly after clearing forests for pasture, in areas of natural forest recovery called "capoeira," which provide a favorable environment for maintaining P. marcgravii growth. Outbreaks of P. marcgravii poisoning coincided with periods of creation of large deforested pastures in the Southeast and Midwest regions of Brazil, and the poisoning should be considered an additional risk after deforestation. The most effective prophylaxis is fencing off the forest areas that contain these plants.

NMR-based metabolomics and bioassays to study phytotoxic extracts and putative phytotoxins from Mediterranean plant species.

INTRODUCTION: Mediterranean plants are characterised by a high content of bioactive secondary metabolites that play important roles in plant-plant interactions as plant growth regulators and could be useful for the development of new eco-friendly herbicides. OBJECTIVE: An NMR-based metabolomics approach was reported to seek selective phytotoxic plant extracts and putative plant-derived active molecules. METHODS: Plant extracts derived from five Mediterranean donor species (Pistacia lentiscus, Bellis sylvestris, Phleum subulatum, Petrohrhagia saxifraga and Melilotus neapolitana) were used to treat the hydroponic cultures of three receiving plants (Triticum durum, Triticum ovatum and Avena fatua). Morphological analyses of the treated receiving plants were carried out. NMR-based metabolomics was applied both to characterise the donor plant extracts and to study the effects of the treatments on the receiving plants. RESULTS: This study allowed the identification of Melilotus neapolitana and Bellis sylvestris as phytotoxic plant and good candidates for further studies. Specifically, the NMR-based metabolomics investigation showed that these species affect a specific set of metabolites (such as sugars, amino and organic acids) and therefore metabolic pathways [i.e. tricarboxylic acid (TCA) cycle, amino acid metabolism, etc.] that are crucial for the plant growth and development. Moreover, it was possible to identify the metabolite(s) probably responsible for the phytotoxicity of the active extracts. CONCLUSION: The NMR-based metabolomics approach employed in this study led to the identification of two phytotoxic plant extracts and their putative active principles. These new insights will be of paramount importance in the future to find plant derived molecules endowed with phytotoxic activities.

Unexplored endemic fruit species from Brazil: Antibiofilm properties, insights into mode of action, and systemic toxicity of four Eugenia spp.

Brazilian endemic fruit species have aroused attention due to their highly valuable, yet unexplored, agro-industrial, food and therapeutic potential. Herein, we describe the antifungal activity of four Eugenia spp. against Candida albicans biofilms, and further demonstrate insights into their potential mode(s) of action and toxicity in vitro and in vivo. Extracts from different parts (seeds, pulps, leaves) of E. leitonii (EL), E. brasiliensis (EB), E. myrcianthes (EM) and E. involucrata (EI) were obtained (S23°23',W45°39') and chemically characterized by GC/MS. The active extracts were tested against C. albicans biofilm viability and architecture, as well as mode of action, and toxicology using RAW 264.7 macrophages and Galleria mellonella larvae. The MIC values ranged from 15.62 to >2000 µg/mL. The most active extracts were EL (seed, 15.62 µg/mL) and EB (leaf and seeds, 31.25 and 15.62 µg/mL, respectively). Treatment with these extracts at 10xMIC reduced biofilm viability by 54-55% (P < 0.0001) as compared to 42% by nystatin. At 10xMIC, all extracts caused damages to biofilm architecture and integrity, and fewer hyphae remained attached to treated biofilms. None of them was found to interfere with cell wall biosynthesis or complexation with ergosterol. The extracts had low toxicity against macrophages in vitro (P > 0.05) and G. mellonella larvae, with mean in vivo LD50 of 1500 mg/kg (EL, seeds); 2500 mg/kg (EB, seeds); and 1250 mg/kg (EB, leaf). The phenolic compounds epicatechin and gallic acid were the major constituents in the extracts. Our findings may open avenues for the application of these yet unexplored native fruits in the food and pharmaceutical industry.

FATAL HONEY POISONING IN SOUTHWEST CHINA: A CASE SERIES OF 31 CASES.

Honey poisoning cases occur in southwestern China. In this case series, we attempted to determine the symptoms and causes of honey poisoning from 2007 to 2012 in southwestern China. We also conducted a quantitative melissopalynological analysis of honey samples. During the study period, 31 honey poisoning cases occurred in the study location, all during July to August. All the cases occurred after consuming at least 100 grams of honey. The most frequent symptoms were nausea and vomiting (100%), abdominal pain (90.3%), diarrhea (74.2%), palpitations (61.3%), dizziness (54.8%), chest congestion (48.4%) and dyspnea (48.4%). Severe cases developed oliguria/anuria, twitch, hematuria, ecchymosis or hematochezia. The median time from ingestion to onset of symptoms was 29 hours. Eight patients died (mortality rate: 25.8%). The pollen of Tripterygium hypoglaucum (a plant with poisonous nectar and pollen) was detected in 22 of 29 honey samples examined (75.9%). The results of pollen analysis were consistent with the clinical findings of previous cases. T. hypoglaucum appears to be the cause of honey poisoning in southwestern China. Honey poisoning should be included in the differential diagnosis of patients who consume honey in this region and develop symptoms of food poisoning.

Potential Health Risks Posed by Plant-Derived Cumulative Neurotoxic Bufadienolides in South Africa.

Bufadienolide-type cardiac glycosides have a worldwide distribution and are mainly synthesized by plants, but there are also animal sources. In South Africa, members of three genera of the Crassulaceae (Cotyledon, Tylecodon and Kalanchoe) cause a unique chronic form of cardiac glycoside poisoning, predominantly in small stock. This paretic/paralytic condition is referred to as "krimpsiekte", cotyledonosis or "nenta". "Krimpsiekte" is a plant poisoning only reported from South Africa and is regarded as the most important plant poisoning of small stock in the semi-arid Little Karoo and southern fringes of the Great Karoo. The toxicosis is caused by cumulative bufadienolides which have neurotoxic properties. Four types of cumulative neurotoxic bufadienolides, namely cotyledoside, and the tyledosides, orbicusides and lanceotoxins, have been isolated. Based on the structure activity relationships and certain toxicokinetic parameters possible reasons for their accumulation are presented. Consumption of edible tissues from animals that have ingested these plants poses a potential risk to humans.

Picrotoxane Sesquiterpene Glycosides and a Coumarin Derivative from Coriaria nepalensis and Their Neurotrophic Activity.

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriarianepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1-3 and five semisynthetic congeners (1a-e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells.

A mixed diet of toxic plants enables increased feeding and anti-predator defense by an insect herbivore.

Some insect herbivores sequester plant secondary metabolites (PSMs) for their own defense, raising the interesting possibility that grazing herbivores are defended by combinations of PSMs from different plant species. In this study, we tested the hypothesis that the grazing caterpillar, Grammia incorrupta, deters the ant, Aphaenogaster cockerelli, by eating a mixture of plants containing iridoid glycosides (IGs) and those containing pyrrolizidine alkaloids (PAs), and that this deterrence is greater than that attained by eating either plant alone. This hypothesis was tested against the non-mutually exclusive hypothesis that mixing plants containing PAs with those containing IGs improves growth performance. Caterpillar survival and growth were measured on three experimental diets: a PA plant, an IG plant, and a mixture of the two. We measured the degree of deterrence associated with these, and an additional experimental diet devoid of PSMs at naturally occurring A. cockerelli nests. Caterpillars fed both plants gained more mass than those fed either plant alone, but took longer to develop. These differences were not caused by diet-based variation in growth efficiency, but by eating more food when offered the mixed-plant diet relative to single-plant diets. The mixed diet was shown to provide deterrence to ants, whereas caterpillars fed single-plant diets were not significantly more deterrent than caterpillars that had eaten the PSM-free diet. We hypothesize that enhanced defense results from increased food consumption in response to multiple plant species, perhaps leading to greater PSM sequestration. Through this mechanism, bottom-up and top-down effects may mutually reinforce the grazing dietary strategy.

Suaveolic acid: a potent phytotoxic substance of Hyptis suaveolens.

Hyptis suaveolens (Lamiaceae) is an exotic invasive plant in many countries. Earlier studies reported that the aqueous, methanol, and aqueous methanol extract of H. suaveolens and its residues have phytotoxic properties. However, to date, the phytotoxic substances of this plant have not been reported. Therefore, the objectives of this study were isolation and identification of phytotoxic substances of H. suaveolens. Aqueous methanol extract of this plant was purified by several chromatographic runs through bioassay guided fractionation using garden cress (Lepidium sativum) as a test plant. Final purification of a phytotoxic substance was achieved by reverse phase HPLC and characterized as 14α-hydroxy-13ß-abiet-8-en-18-oic acid (suaveolic acid) by high-resolution ESI-MS, (1)H-,(13)C-NMR, CD, and specific rotation. Suaveolic acid inhibited the shoot growth of garden cress, lettuce (Lactuca sativa), Italian ryegrass (Lolium multiflorum), and barnyard grass (Echinochloa crus-galli) at concentrations greater than 30 µM. Root growth of all but lettuce was also inhibited at concentrations greater than 30 µM. The inhibitory activities were concentration dependent. Concentrations required for 50% growth inhibition of suaveolic acid for those test plant species were ranged from 76 to 1155 µM. Therefore, suaveolic acid is phytotoxic and may be responsible for the phytotoxicity of H. suaveolens plant extracts.

Fatal Wedelia glauca intoxication in calves following natural exposure.

A group of 342 beef calves, corralled in the Patagonia region of Argentina, were fed alfalfa hay that had been inadvertently contaminated with Wedelia glauca. A total of 147 (43%) calves died within 4 days. Pathologic findings in 2 calves were diffuse centrilobular hepatic necrosis and hemorrhage with edema in the gallbladder, common bile duct, and choledochoduodenal junction. Epidermal fragments of W. glauca were identified in rumen contents by microscopy. Intact W. glauca plants and leaf fragments were found in the hay. Patches of defoliated W. glauca were also identified in the alfalfa pasture from which the hay had been baled.

Effect of the administration of young leaves of Quercus pyrenaica on rumen fermentation in relation to oak tannin toxicosis in cattle.

Three experiments were conducted to study the effect of the administration of young leaves of Quercus pyrenaica (OL) on in vivo ruminal fermentation in relation to oak tannin toxicosis in cattle. In Experiment 1, six bulls were fed up to 5 kg fresh matter (FM) of OL per animal and day for 14 days. In Experiment 2, another six bulls were first subjected to severe feed restriction for 8 days and then fed a higher amount of OL (approximately 10 kg FM daily) for 3 days. In Experiment 3, three bulls received the same amount of OL as in Experiment 1 for 6 days, but adding a severe feed restriction as in Experiment 2. In situ DM disappearance of grass hay and OL, and pH and ammonia and volatile fatty acid concentrations were recorded throughout the three assays. Daily administration of up to 5 kg OL did not considerably affect ruminal fermentation, unless it was preceded by a severe feed restriction period. Administration of 10 kg OL preceded by undernutrition triggered a critical reduction in rumen fermentation activity concomitantly with an acute intoxication. Interestingly, some results differ from those observed previously in vitro, which highlights the importance of validating in vitro data with in vivo measurements, given the complexity of extrapolation in ruminants.

Elucidating the neurotoxicity of the star fruit.

Caramboxin: Patients suffering from chronic kidney disease are frequently intoxicated after ingesting star fruit. The main symptoms of this intoxication are named in the picture. Bioguided chemical procedures resulted in the discovery of caramboxin, which is a phenylalanine-like molecule that is responsible for intoxication. Functional experiments in vivo and in vitro point towards the glutamatergic ionotropic molecular actions of caramboxin, which explains its convulsant and neurodegenerative properties.

A review of poisonous plants that cause reproductive failure and malformations in the ruminants of Brazil.

The objective of this review is to provide a report on toxic plants causing reproductive problems in ruminants in Brazil. Aspidosperma pyrifolium causes abortion or stillbirth in goats, as well as most likely in sheep and cattle, in the semiarid regions of Northeastern Brazil. Intoxications by Ateleia glazioveana, Tetrapterys acutifolia and T. multiglandulosa result in abortion and neonatal mortality in cattle and sheep, and the same signs have been experimentally observed in goats. These three plants can also cause cardiac fibrosis and a nervous disease with spongiosis of the central nervous system. Other plants known to cause abortion include Enterolobium contortisiliquum, E. gummiferum, Stryphnodendron coriaceum, S. obovatum and S. fissuratum. These plants can also cause digestive signs and photosensitization. Abortions have been reported in animals intoxicated by nitrates and nitrites as well. Infertility, abortions and the birth of weak offspring have been reported in animals intoxicated by plants containing swainsonine, including Ipomoea spp., Turbina cordata and Sida carpinifolia. Trifolium subterraneum causes estrogenism in cattle. Mimosa tenuiflora and, most likely, M. ophthalmocentra cause malformations and embryonic mortality in goats, sheep and cattle in the semiarid regions of Northeastern Brazil.

Consumption of nephrotoxic plants among chronic hemodialysis patients in the Eastern region of Morocco: A multicentric cross-sectional study.

ETHNOPHARMACOLOGICAL RELEVANCE: The consumption of nephrotoxic plants is quite frequent in Morocco and could explain the high prevalence of indeterminate nephropathy in patients with End-Stage Kidney Disease (ESKD). AIM OF THE STUDY: to determine, in a population of chronic hemodialysis (CHD) patients and before the occurrence of ESKD, the prevalence of the use of nephrotoxic plants, in particular, Aristolochia longa L. (Bereztam) and the etiological role of plants in the rapid progression of known and unknown nephropathy toward the end stage of chronic hemodialysis. MATERIALS AND METHODS: This was a multicentric cross-sectional study spread over 12 months (May 2019-May 2020), carried out in public hemodialysis centers in the eastern region of Morocco. Clinical data were collected from medical records. Herbal and sociodemographic data were collected from a detailed and precise interview with each enrolled CHD patient. RESULTS: A total of 404 CHD patients participated in the study. 71.5%, had used medicinal plants before the occurrence of ESKD and 32.9% had indeterminate nephropathy. Among the plants consumed, we identified plants whose kidney toxicity was well demonstrated, mainly Rhamnus alaternus L. (Mlilas) in 66.7%, Artemisia herba alba Asso (Chih) in 54.32%, Aristolochia longa L.(Bereztam) in 52.6%, and Rubia tinctorum L. (Fowa) in 47.4%. 27.7% of CHD patients had presented complications following the use of the plants before the occurrence of ESKD. In multivariate analysis, the use of plants to treat digestive disorders (OR 9.57; 95%CI [4.49-20.37], P < 0.001) and asthenia associated with anemia (OR 8.59; 95%CI [3.92-18.81], P < 0.001), as well as side effects observed after taking the plants (OR 4; 95%CI [1.09, 14.7], P = 0.03), were identified as significant risk factors for the occurrence of severe indeterminate nephropathy. CONCLUSIONS: This study showed the high prevalence of consumption of nephrotoxic herbs which may be the root cause of chronic renal failure in CHD patients.

Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum.

BACKGROUND & AIMS: One major cause of hepatic sinusoidal obstruction syndrome (HSOS) is the intake of pyrrolizidine alkaloid (PA)-containing products. Over 8000 PA-induced HSOS cases have been reported worldwide and at least 51 among them were suspected to be attributed to exposure to the Chinese medicine 'Tusanqi'. PA-induced hepatotoxicity involves cytochrome P450-mediated metabolic activation of PAs to electrophilic pyrrolic metabolites which react with macromolecules, such as proteins. However, no studies have found such protein adduction in HSOS patients. We report one HSOS case confirmed by liver biopsy, where the patient claimed taking 'Tusanqi' as self-medication. METHODS: The herb was analyzed by HPLC-MS, and its induced hepatotoxicity in rats was assessed by monitoring the alteration of serum ALT level and liver morphology. Blood pyrrole-protein adducts were determined by UPLC-MS. RESULTS: The herb the patient consumed was identified as Gynura segetum, an erroneous substitute of non-PA-containing Sedum aizoon, called 'Tusanqi'. Hepatotoxic PAs senecionine and seneciphylline were detected in G. segetum. In the PA-exposed patient, serum pyrrole-protein adducts were detected by a newly developed analytical approach. The animal study showed a good correlation of liver injury with the ingestion of G. segetum. CONCLUSIONS: For the first time, serum pyrrole-protein adducts were unequivocally detected in a PA-induced HSOS patient, and such adducts show a potential to be developed as a biomarker for the assessment of PA-induced HSOS. Similar to the well-known case of aristolochic acid-poisoning, the observed HSOS was confirmed to arise from the consumption of PA-containing G. segetum, an erroneous substitute of non-PA-containing S. aizoon.

Alpha-adrenergic receptor blocking effect of Cleistanthus collinus (Roxb.) Benth. and Hook f. leaf extract on guinea pig isolated smooth muscle preparations.

Aqueous extract of C. collinus leaves inhibited norepinephrine induced contraction in guinea pig vas deferens and aortic strip in a dose-dependent manner. Inhibition of acetylcholine induced contraction in ileum was dose independent. C. collinus extract per se had no effect on isolated guinea pig vas deferens and aortic strip, but inhibited norepinephrine induced contraction in a dose-dependent manner probably by its antagonist action on alpha-adrenergic receptor. It had inconsistent effect on guinea pig ileum in vitro preparation.

Acaricidal efficacy against cattle ticks and acute oral toxicity of Lippia javanica (Burm F.) Spreng.

In search for low-cost, safe and environmentally benign plant-based alternatives to commercial pesticides, the efficacy of Lippia javanica aqueous leaf extracts in controlling ticks on cattle, acute oral toxicity in mice and phytochemistry were evaluated. L. javanica aqueous leaf extracts at 10% and 20% w/v were effective at controlling cattle ticks but not as good as an amitraz-based acaricide Tickbuster. However, they can provide an effective tick control option where synthetic products are unavailable or unaffordable, particularly in remote parts of southern Africa. Peripheral blood samples collected showed no haemoparasites in treated cattle implying that animals did not suffer from clinical tick-borne diseases. The leaf aqueous extracts of L. javanica were tested for toxicity in BALB/c mice. While anecdotal evidence suggests L. javanica has low mammalian toxicity, within 48 h all mice fed with the L. javanica leaf aqueous extract at 12.5-37.5% v/v were lethargic, and overall mortality was 37.5% (n = 24). Thus, despite their apparent safety, water extracts of L. javanica leaves may have deleterious health implications on humans and animals if consumed at very high doses. Many compounds have been identified from L. javanica including an array of phenolic glycosides, flavonoids and essential oils but none of these are known to have acute toxic properties.

Glycocluster design for improved avidity and selectivity in blocking human lectin/plant toxin binding to glycoproteins and cells.

Blocking lectin/toxin binding to human cells by suitable inhibitors can therapeutically protect them from harmful effects. Clustered design of ligand presentation holds the promise of affinity increase relative to the free sugar and inherent selectivity among lectin targets. Using first a solid-phase assay with a glycoprotein presenting N-glycans as lectin-reactive probe, we assessed the inhibitory potency of bi- to tetravalent clusters on a plant toxin and three human adhesion/growth-regulatory lectins. Enhanced avidity relative to the free sugar was detected together with lectin-type selectivity. These effects were confirmed on the level of cells in vitro, also for two leguminous lectins. The lack of toxicity in cell proliferation assays excluded concerns to further work on these compounds. The given cluster design and the strategic combination of the two assay systems of increasing biorelevance will thus be helpful to take the next steps in drug development, e.g. tailoring the sugar headgroup.