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.

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.

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.

Rapid identification of herbal toxins using electrospray laser desorption ionization mass spectrometry for emergency care.

The unintentional ingestion of toxic compounds in herbs is not uncommon in many parts of the world. To provide timely and life-saving care in the emergency department, it is essential to develop a point-of-care analytical method that can rapidly identify these toxins in herbs. Since electrospray laser desorption ionization mass spectrometry (ELDI/MS) has been successfully used to characterize non-volatile chemical compounds without sample preparation, it was used to identify toxic herbal compounds in this study. The herbal toxins were collected either by sweeping a metallic probe across the surface of a freshly cut herb section or by directly sampling extracts of ground herbal powder. The analytes on the probe were then desorbed, ionized and detected using ELDI/MS, wherein analysis of the herbal toxins was completed within 30 s. This approach allows for the rapid morphological recognition of herbs and early point-of-care identification of herbal toxins for emergency management and is promising in providing important toxicological information to ensure appropriate medical treatment.

The problem of misidentification between edible and poisonous wild plants: Reports from the Mediterranean area.

Today, in many European countries, people are looking for wild edible plants to experience new tastes and flavors, by following the new trend of being green and environmentally friendly. Young borage and spinach leaves can be easily confused by inexpert pickers with those of other plants, including poisonous ones, such as Mandragora autumnalis Bertol. (mandrake) or Digitalis purpurea L. (foxglove), common in southern and northern Italy respectively. In the last twenty years, several cases of intoxication by accidental ingestion of mandrake and foxglove have been reported. The purpose of this work was to perform a pharmacognostic characterization of young leaves from borage, mandrake, foxglove and spinach, by micro-morphological, molecular and phytochemical techniques. The results showed that each of the three techniques investigated could be sufficient alone to provide useful information for the identification of poisonous species helping the medical staff to manage quickly the poisoned patients. However, the multi-disciplinary approach proposed could be very useful to asses the presence of poisonous plants in complex matrices, to build a database containing morphological, molecular and phytochemical data for the identification of poisonous species or in forensic toxicology, given their increasingly frequent use due to their low cost and relatively common availability.

Atropa belladonna neurotoxicity: Implications to neurological disorders.

Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at-risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults, and animal models as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders.

Yellow Oleander Seed, or "Codo de Fraile" (Thevetia spp.): A Review of Its Potential Toxicity as a Purported Weight-Loss Supplement.

The Dietary Supplements and Health Education Act (DSHEA), passed by the United States Congress in October of 1994, defines herbal products as nutritional supplements, not medications. This opened the market for diverse products made from plants, including teas, extracts, essential oils, and syrups. Mexico and the United States share an extensive border, where diverse herbal products are available to the public without a medical prescription. Research undertaken in the neighboring cities of Ciudad Juarez, Mexico, and El Paso, Texas, USA, shows the use of herbs is higher in this border area compared to the rest of the United States. A portion of the population is still under the erroneous impression that "natural" products are completely safe to use and therefore lack side effects. We review the dangers of ingesting the toxic seed of Thevetia spp. (family Apocynaceae), commonly known as "yellow oleander" or "codo de fraile," misleadingly advertised on the Internet as an effective and safe dietary supplement for weight loss. Lack of proper quality control regarding herbs generates a great variability in the quantity and quality of the products' content. Herb-drug interactions occur between some herbal products and certain prescription pharmaceuticals. Certain herbs recently introduced into the U.S. market may not have been previously tested adequately for purity, safety, and efficacy. Due to the lack of reliable clinical data regarding the safe use of various herbal products currently available, the public should be made aware regarding the possible health hazards of using certain herbs for therapeutic purposes. The potentially fatal toxicity of yellow oleander seed is confirmed by cases reported from various countries, while the purported benefits of using it for weight loss have not been evaluated by any known clinical trials. For this reason, the use of yellow oleander seed as a dietary supplement should be avoided.

A Simple and Fast Procedure to Determine 3-Nitropropanoic Acid and 3-Nitropropanol in Freeze Dried Canadian Milkvetch (Astragalus canadensis).

Canadian milkvetch (Astragalus canadensis) is a North American plant species in the legume family and some of this plant is fatally poisonous to livestock. The poisoning is attributed to the natural occurrence of notrotoxins, i.e., 3-nitropropanoic acid and 3-nitropropanol, present as aglycones and conjugated forms in the plant. Those compounds cause nitrite oxidization of hemoglobin and inhibition of cellular metabolism. To determine the toxicity of the plant, it is very important to develop an analytical method for the contents of the compounds in the plant. In this study, we have successfully developed an extraction procedure followed by HPLC-UV analysis to simultaneously analyze notrotoxins. The aglycones could be released from its conjugated forms in the freeze dried plant and extracted by water at room temperature. An HPLC-UV method using a Phenomenex Kinetex 2.6 µ F5 100 Å 100 × 4.6 mm column with pH 3.5 phosphonate buffer as mobile phase have been developed and validated for the detection of the two compounds at 210 nm. This developed procedure for the analysis of 3-nitropropanoic acid and 3-nitropropanol has proven simple and efficient and it has been successfully applied for batch sample analysis.

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.

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.

Therapeutic values, chemical constituents and toxicity of Taiwanese Dysosma pleiantha--a review.

Dysosma pleiantha (Hance) Woodson also called as Bajiaolian belongs to the family Berberidaceae, is widely used in Taiwan as traditional Chinese herbal medicine for more than thousands of years. It is usually recommended by various traditional Chinese medical doctors and herbal pharmacies for general remedies including postpartum recovery, treatment of weakness, neck mass, acne, hepatoma, lumbago, snakebite, tumor growth and dysmenorrhea. In the textbooks of traditional Chinese medicine, there is limited information about the toxicity of Bajiaolian. Podophyllotoxin, a lignan is the main toxic ingredient of Bajiaolian rhizome. Therefore, Bajiaolian is documented as the fifth highest cause of poisoning among the herbal medicine in Taiwan. Since the therapeutic and toxic doses are very close, Bajiaolian poisoning cases are frequently reported in Taiwan. Moreover, Dysosma poisoning cases are difficult to diagnosis because physicians are unfamiliar with this medicine's multiple clinical presentations in different stages of intoxication. Therefore, the objective of this review is to represent the collective information available in literatures regarding D. pleiantha, a cytotoxic lignan containing medicinal plant. Specifically, the literatures have been reviewed for articles pertaining to chemical constituents, properties, therapeutical benefits, toxicity, poisoning symptoms, toxic as well as therapeutic dose and medical management.

Important poisonous plants in tibetan ethnomedicine.

Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms of their significance in traditional Tibetan medicinal practices. They are Aconitum pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for which the toxic chemical constituents, bioactivities and pharmacological functions are reviewed herein. The most important toxins include aconitine, strychnine, scopolamine, and anisodamine. These toxic plants are still currently in use for pain-reduction and other purposes by Tibetan healers after processing.

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.

Secondary compounds in floral rewards of toxic rangeland plants: impacts on pollinators.

The study of plant secondary chemistry has been essential in understanding plant consumption by herbivores. There is growing evidence that secondary compounds also occur in floral rewards, including nectar and pollen. Many pollinators are generalist nectar and pollen foragers and thus are exposed to an array of secondary compounds in their diet. This review documents secondary compounds in the nectar or pollen of poisonous rangeland plants of the western United States and the effects of these compounds on the behavior, performance, and survival of pollinators. Furthermore, the biochemical, physiological, and behavioral mechanisms by which pollinators cope with secondary compound consumption are discussed, drawing parallels between pollinators and herbivores. Finally, three avenues of future research on floral reward chemistry are proposed. Given that the majority of flowering plants require animals for pollination, understanding how floral reward chemistry affects pollinators has implications for plant reproduction in agricultural and rangeland habitats.

Phytochemicals and biological activities of poisonous genera of Ericaceae in China.

The family Ericaceae is comprised of about 70 genera of which about 20 are found throughout China. Of these Ledum, Rhododendron, Enkianthus, Pieris, Craibiodendron, Gaultheria, Vaccinium, and Leucothoe are regarded as poisonous. Many species of these poisonous genera are used as Chinese herbal medicines for the treatment of, for example, inflammation, asthma, and coughs. Modem research has demonstrated that the toxic ingredients of these poisonous genera are chiefly tetracyclic diterpenes, which have adverse effects on the digestive, cardiovascular and nervous systems. Because various species of these poisonous genera also have medicinal functions, extensive studies of these plants have led to the identification of many kinds of compound. This paper compiles 306 compounds from the eight poisonous genera, reported in 141 references.

Targeted analysis of multiple pharmaceuticals, plant toxins and other secondary metabolites in herbal dietary supplements by ultra-high performance liquid chromatography-quadrupole-orbital ion trap mass spectrometry.

In this study, an ultra-high performance liquid chromatography-quadrupole-orbital ion trap mass spectrometry (UHPLC-Q-orbitrap MS) method was developed and validated for simultaneous determination of 96 pharmaceuticals, plant toxins, and other plant secondary metabolites in herbal dietary supplements. Target analytes were extracted from samples using the QuEChERS (quick easy cheap effective rugged safe) procedure. The instrument was operated in full MS-data dependent tandem mass spectrometry (full MS-dd-MS/MS) acquisition mode which enabled collection of quantitative high resolution (HR) full mass spectral data and confirmatory HR MS/MS data in a single run. The method provided excellent selectivity in both full MS and dd-MS/MS mode. Under optimized collision energy settings, product ion spectra containing both precursor and two or more product ions were obtained for most of the analytes. Limits of detection (LODs) and limits of quantification (LOQs) for the method differed significantly for the examined matrices. LODs≤10µg kg(-1) and LOQs≤50µg kg(-1) were obtained for 48 to 81% of target compounds across five different matrices. With the exception of highly polar analytes, the optimized QuEChERS extraction procedure provided acceptable recoveries in the range 70%-120%. The precision of the method, characterized as the relative standard deviation (RSD, n=5), was ≤25% and ≤18% at spiking concentrations of 50µg kg(-1) and 500µg kg(-1), respectively. Because of variations in matrix effects in extracts of herbal dietary supplements that differed in composition, the method of standard additions and an approach based on dilution of matrix components followed by quantification using solvent standards were applied for quantification. The procedure was used to examine commercial dietary supplements for the 96 analytes of interest. To the best of our knowledge, this is the first report of an integrated analysis and quantification of this wide range of compounds.

Traditional knowledge on poisonous plants of Udhampur district of Jammu and Kashmir, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Poisonous plants comprise the third largest category of poisons known around the world. Other than affecting the humans directly, they are the major cause of economic losses in the livestock industry since the advent of civilisation. Aim of the present study was to collect and systematically document the traditional knowledge of poisonous plants of Udhampur District for the benefit of humanity before it is entombed forever. MATERIAL AND METHODS: Direct interviews of the informants were conducted and the plants identified as poisonous by them were collected, identified and herbarium sheets were prepared. The data collected through interviews was analysed with two quantitative tools viz. the factor informant consensus and fidelity level. RESULTS: A total of 90 toxic plants were listed from the study site. Most dominant toxic families were Fabaceae, Asteraceae, Solanaceae, Apocynaceae and Euphorbiaceae. Most of the poisonous plants were herbs (57.1%) and the whole plant toxicity was reported to be the highest (32.4%) followed by leaves (23.1%). According to the factor informant consensus, gastrointestinal category had the greatest agreement closely followed by the death category. The most important species on the basis of fidelity level for gastrointestinal category were Cannabis sativa, Cassia occidentalis, Cuscuta reflexa, Euphorbia helioscopia and Euphorbia hirta, for death category were Anagalis arvensis, Embelia robusta and Prunus persica, for dermatological category Euphorbia royleana, Leucaena leucocephala, Parthenium hysterophorus and Urtica dioica, and for sexual illness category were Calotropis procera and Carica papaya. CONCLUSION: Further phytochemical and pharmacological studies are required to ascertain the toxic components of the poisonous plants, so that they may be utilised for the betterment of future generations.