Topical Collection "Toxicity of Natural Alkaloids"

A topical collection in Toxins (ISSN 2072-6651). This collection belongs to the section "Plant Toxins".

Editor

Dr. Kevin Welch
E-Mail
Collection Editor
USDA/ARS, Poisonous Plant Research Lab, 1150 East 1400 North Logan, Utah 84341, USA
Interests: To evaluate the toxicity of plant toxins in livestock, describe the toxicokinetics of plant toxins, characterize the molecular alterations due to plant toxins, identify diagnostic biomarkers of intoxication, including the degree and duration of intoxication, and develop methods to predict a prognosis for recovery

Topical Collection Information

Dear Colleagues,

Poisonous plants, and the toxins they produce, result in major economic losses to livestock industries throughout the world. Several of these plants are also toxic to humans. The toxic components of many of the more problematic poisonous plants are alkaloids. There are numerous classes of alkaloids, grouped by chemical structure, including pyrrolizidine, piperidine, pyridine, indole, quinolizidine, indolizidine, diterpenoid, tropane, and steroidal alkaloids. In this Special Issue, various aspects of the toxicity of numerous alkaloids from plants will be discussed. This Special Issue welcomes contributions of both reviews and original research on the toxicity of natural alkaloids, especially alkaloids produced by plants.

Dr. Kevin Welch
Collection Editor

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. The article processing charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs).

Keywords

  • poisonous plants
  • plant alkaloids
  • plant toxins
  • pyrrolizidine alkaloids
  • piperidine alkaloids
  • pyridine alkaloids
  • indole alkaloids
  • quinolizidine alkaloids
  • indolizidine alkaloids
  • diterpenoid alkaloids
  • tropane alkaloids
  • steroidal alkaloids

Published Papers (15 papers)

2020

Jump to: 2018, 2017, 2016, 2015

Review
Extracting and Analyzing Pyrrolizidine Alkaloids in Medicinal Plants: A Review
Toxins 2020, 12(5), 320; https://doi.org/10.3390/toxins12050320 - 13 May 2020
Cited by 9 | Viewed by 1492
Abstract
Pyrrolizidine alkaloids (PAs) are distributed in plant families of Asteraceae, Boraginaceae, and Fabaceae and serve in the chemical defense mechanism against herbivores. However, they became a matter of concern due to their toxicity associated with the high risk of intake within herbal [...] Read more.
Pyrrolizidine alkaloids (PAs) are distributed in plant families of Asteraceae, Boraginaceae, and Fabaceae and serve in the chemical defense mechanism against herbivores. However, they became a matter of concern due to their toxicity associated with the high risk of intake within herbal preparations, e.g., phytopharmaceutical formulations, medicinal teas, or other plant-derived drug products. In 1992, the German Federal Ministry of Health established the first limits of PA content for fourteen medicinal plants. Because of the toxic effects of PAs, the Federal Institute of Risk Assessment (BfR) established more stringent limits in 2011, whereby a daily intake <0.007 µg/kg body weight was recommended and valid until 2018. A threefold higher limit was then advised by BfR. To address consumer safety, there is the need for more efficient extraction procedures along with robust, selective, and sensitive analytical methods to address these concerns. With the increased prevalence of, e.g., phytopharmaceutical formulations, this timely review comprehensively focuses on the most relevant extraction and analysis strategies for each of those fourteen plant genera. While a variety of extraction procedures has been reported, differences in PA content of up to 1110 ppm (0.11% (w/w)) were obtained dependent on the nature of the solvent and the applied extraction technique. It is evident that the efficient extraction of PAs requires further improvements or at least standardization of the extraction conditions. Comparing the various analytical techniques applied regarding selectivity and sensitivity, LC-MS methods appear most suited. This review shows that both standardized extraction and sensitive determination of PAs is required for achieving appropriate safety levels concerning public health in future. Full article
Show Figures

Figure 1

2018

Jump to: 2020, 2017, 2016, 2015

Article
Sublethal Effects of Solanum nigrum Fruit Extract and Its Pure Glycoalkaloids on the Physiology of Tenebrio molitor (Mealworm)
Toxins 2018, 10(12), 504; https://doi.org/10.3390/toxins10120504 - 01 Dec 2018
Cited by 6 | Viewed by 1251
Abstract
Background: Solanaceae plants produce glycoalkaloids (GAs) that affect various physiological processes of herbivorous insects and they are being tested as potential alternatives for synthetic pesticides. They cause lethal and sublethal effects. Nevertheless, their mode of action remains unclear. Therefore, we examined the effects [...] Read more.
Background: Solanaceae plants produce glycoalkaloids (GAs) that affect various physiological processes of herbivorous insects and they are being tested as potential alternatives for synthetic pesticides. They cause lethal and sublethal effects. Nevertheless, their mode of action remains unclear. Therefore, we examined the effects of Solanum nigrum fruit extracts and pure glycoalkaloids on a model beetle, Tenebrio molitor. Methods: Plant extracts or pure alkaloids were added to the food of the larvae for three days. The lipid, glycogen, and protein content in the fat body and the midgut were determined, and the contractility of the heart, hindgut, and oviduct muscles was tested using the video-microscopy technique. Finally, the ultrastructure of the fat body and the midgut was observed using electron microscopy. Results: No lethal effects were noted. Sublethal changes were observed in the content of biomolecules, malformations of organelles, chromatin condensation, and heart and oviduct contractility. The observed effects differed between the tested glycoalkaloids and the extract. Conclusions: Both the extract and pure GAs have a wide range of effects that may result in impaired development, food intake, and reproduction. Some early effects may be used as bioindicators of stress. The effects of the extract and pure alkaloids suggest that the substances produced by the plant may act additively or synergistically. Full article
Show Figures

Figure 1

2017

Jump to: 2020, 2018, 2016, 2015

Review
Worldwide Occurrence and Investigations of Contamination of Herbal Medicines by Tropane Alkaloids
Toxins 2017, 9(9), 284; https://doi.org/10.3390/toxins9090284 - 15 Sep 2017
Cited by 6 | Viewed by 3424
Abstract
Tropane alkaloids occur mainly in Solanaceae plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic poisoning due to the contamination of herbal teas and herbs by tropane alkaloids. Tropane alkaloid poisoning can occur after [...] Read more.
Tropane alkaloids occur mainly in Solanaceae plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic poisoning due to the contamination of herbal teas and herbs by tropane alkaloids. Tropane alkaloid poisoning can occur after consumption of any medicinal plant if Solanaceae plants or plant parts are present as contaminants. Globally, almost all reports in 1978–2014 involve herbal teas and one of the prescribed herbs in composite formulae. Contamination most likely occurs during harvest or processing. As for prescribed herbs, on-site inspection is necessary to exclude cross-contamination and accidental mix-up at the retail level. The diagnosis is confirmed by screening for the presence of Solanaceae species and tropane alkaloids. Herbal teas and herbs contaminated by tropane alkaloids can pose a serious health hazard because these relatively heat-stable alkaloids may exist in large quantities. The WHO repeatedly emphasises the importance of good agricultural and collection practices for medicinal plants. DNA barcoding is increasingly used to exclude the presence of contaminants (particularly toxic species) and product substitution. All suspected cases should be reported to health authorities so that investigations along the supply chain and early intervention measures to protect the public can be initiated. Full article
Show Figures

Figure 1

2016

Jump to: 2020, 2018, 2017, 2015

Review
Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity
Toxins 2016, 8(12), 356; https://doi.org/10.3390/toxins8120356 - 29 Nov 2016
Cited by 23 | Viewed by 3210
Abstract
Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication [...] Read more.
Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. Full article
Show Figures

Figure 1

Article
Vasoactivity and Vasoconstriction Changes in Cattle Related to Time off Toxic Endophyte-Infected Tall Fescue
Toxins 2016, 8(10), 271; https://doi.org/10.3390/toxins8100271 - 22 Sep 2016
Cited by 18 | Viewed by 2297
Abstract
Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time [...] Read more.
Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture. In Experiment 1, lateral saphenous vein biopsies were conducted on 21 predominantly Angus steers (357 ± 3 kg body weight) at 0 (n = 6), 7 (n = 6), 14 (n = 5), or 28 days (n = 4) after removal from grazing pasture (3.0 ha; endpoint ergovaline + ergovalinine = 1.35 mg/kg DM) for 126 days. In Experiment 2, lateral saphenous veins were biopsied from 24 Angus-cross steers (361 ± 4 kg body weight) at 0, 21, 42, and 63 days (n = 6 per time point) following removal from grazing tall fescue pastures (3.0 ha; first 88 days endpoint ergovaline + ergovalinine = 0.15 mg/kg DM; last 18 days endpoint ergovaline + ergovalinine = 0.57 mg/kg DM) for 106 total days. Six steers (370 ± 18 kg body weight) off of bermudagrass pasture for the same time interval were also biopsied on Day 0 and Day 63 (n = 3 per time point). Additionally, in Experiment 2, cross-sectional ultrasound scans of caudal artery at the fourth coccygeal vertebra were taken on Days 0, 8, 15, 21, 29, 36, 42, and 45 to determine mean artery luminal area to evaluate vasoconstriction. In both experiments, steers were removed from pasture and housed in a dry lot and fed a corn silage diet for the duration of biopsies and ultrasound scans. Biopsied vessels used to evaluate vasoactivity were cleaned, incubated in a multimyograph, and exposed to increasing concentrations of 4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide (TCB2; 5HT2A agonist), guanfacine (GF; α2A-adrenergic agonist), and (R)-(+)-m-nitrobiphenyline oxalate (NBP; α2C-adrenergic agonist) in both experiments and ergovaline (ERV) and ergotamine (ERT) in Experiments 1 and 2, respectively. In Experiment 1, days off pasture × agonist concentration was not significant (p > 0.1) for all four compounds tested. In Experiment 2, GF, NBP, TCB2 and ERT were significant for days off pasture × agonist concentration interaction (p < 0.02) and vasoactivity increased over time. Vasoactivity to agonists was reduced (p < 0.05) when steers were initially removed from E+ tall fescue pasture compared to bermudagrass, but did not differ by Day 63 for any variable. Luminal areas of caudal arteries in steers grazed on E+ tall fescue relaxed and were similar to steers that had grazed bermudagrass for 36 days on non-toxic diet (p = 0.15). These data demonstrate changes in peripheral vasoactivity and recovery from vasoconstriction occur beyond five weeks off toxic pasture and 5HT2A receptors appear to be more dramatically affected in the lateral saphenous vein by grazing E+ tall fescue pasture than adrenergic receptors. Full article
Show Figures

Figure 1

Article
Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids
Toxins 2016, 8(7), 204; https://doi.org/10.3390/toxins8070204 - 04 Jul 2016
Cited by 3 | Viewed by 2478
Abstract
Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and [...] Read more.
Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. Full article
Show Figures

Graphical abstract

Review
Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong
Toxins 2016, 8(3), 80; https://doi.org/10.3390/toxins8030080 - 18 Mar 2016
Cited by 8 | Viewed by 2610
Abstract
In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989–2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data [...] Read more.
In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989–2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989–1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994–1996. In the whole of Hong Kong, the incidence during 2000–June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008–2012 was 0.06 per 100,000 population. Contamination of non-toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures. Full article
Article
Maternal Ingestion of Ipomoea carnea: Effects on Goat-Kid Bonding and Behavior
Toxins 2016, 8(3), 74; https://doi.org/10.3390/toxins8030074 - 16 Mar 2016
Cited by 6 | Viewed by 2667
Abstract
Ipomoea carnea is a toxic plant found in Brazil and other tropical and subtropical countries and often causes poisoning of livestock. The plant contains the alkaloids swainsonine and calystegines, which inhibit key cellular enzymes and cause systematic cell death. This study evaluated the [...] Read more.
Ipomoea carnea is a toxic plant found in Brazil and other tropical and subtropical countries and often causes poisoning of livestock. The plant contains the alkaloids swainsonine and calystegines, which inhibit key cellular enzymes and cause systematic cell death. This study evaluated the behavioral effects of prenatal ingestion of this plant on dams and their kids. Twenty-four pregnant goats were randomly allocated into four treatment groups and received the following doses (g/kg BW) of fresh I. carnea: 0 (control group), 1.0 (IC1), 3.0 (IC3), and 5.0 (IC5) from day 27 of gestation until parturition. Dam and kid bonding and behavior were evaluated by several tests, immediately after birth until six weeks of age. Dams from IC3 and IC5 groups spent less time paying attention to the newborn. There was a lack of maternal-infant bonding due to I. carnea intoxication. Kids from treated dams had difficulty in standing, suckling, and in recognizing their mother hours after birth. I. carnea can also compromise the kids’ ability to learn and to retain spatial memory. We suggest that kids from pregnant goats given I. carnea during gestation have significant behavioral alterations and developmental delays that may compromise their survival. Full article
Show Figures

Graphical abstract

Review
A Review of Bioinsecticidal Activity of Solanaceae Alkaloids
Toxins 2016, 8(3), 60; https://doi.org/10.3390/toxins8030060 - 01 Mar 2016
Cited by 88 | Viewed by 6135
Abstract
Only a small percentage of insect species are pests. However, pest species cause significant losses in agricultural and forest crops, and many are vectors of diseases. Currently, many scientists are focused on developing new tools to control insect populations, including secondary plant metabolites, [...] Read more.
Only a small percentage of insect species are pests. However, pest species cause significant losses in agricultural and forest crops, and many are vectors of diseases. Currently, many scientists are focused on developing new tools to control insect populations, including secondary plant metabolites, e.g., alkaloids, glycoalkaloids, terpenoids, organic acids and alcohols, which show promise for use in plant protection. These compounds can affect insects at all levels of biological organization, but their action generally disturbs cellular and physiological processes, e.g., by altering redox balance, hormonal regulation, neuronal signalization or reproduction in exposed individuals. Secondary plant metabolites cause toxic effects that can be observed at both lethal and sublethal levels, but the most important effect is repellence. Plants from the Solanaceae family, which contains numerous economically and ecologically important species, produce various substances that affect insects belonging to most orders, particularly herbivorous insects and other pests. Many compounds possess insecticidal properties, but they are also classified as molluscides, acaricides, nematocides, fungicides and bactericides. In this paper, we present data on the sublethal and lethal toxicity caused by pure metabolites and crude extracts obtained from Solanaceae plants. Pure substances as well as water and/or alcohol extracts cause lethal and sublethal effects in insects, which is important from the economical point of view. We discuss the results of our study and their relevance to plant protection and management. Full article
Show Figures

Graphical abstract

Review
Lolitrem B and Indole Diterpene Alkaloids Produced by Endophytic Fungi of the Genus Epichloë and Their Toxic Effects in Livestock
Toxins 2016, 8(2), 47; https://doi.org/10.3390/toxins8020047 - 15 Feb 2016
Cited by 33 | Viewed by 3424
Abstract
Different group of alkaloids are produced during the symbiotic development of fungal endophytes of the genus Epichloë in grass. The structure and toxicity of the compounds vary considerably in mammalian herbivores and in crop pests. Alkaloids of the indole-diterpene group, of which lolitrem [...] Read more.
Different group of alkaloids are produced during the symbiotic development of fungal endophytes of the genus Epichloë in grass. The structure and toxicity of the compounds vary considerably in mammalian herbivores and in crop pests. Alkaloids of the indole-diterpene group, of which lolitrem B is the most toxic, were first characterized in endophyte-infected perennial ryegrass, and are responsible for “ryegrass staggers.” Ergot alkaloids, of which ergovaline is the most abundant ergopeptide alkaloid produced, are also found in ryegrass, but generally at a lower rate than lolitrem B. Other alkaloids such as lolines and peramine are toxic for crop pests but have weak toxicological properties in mammals. The purpose of this review is to present indole-diterpene alkaloids produced in endophyte infected ryegrass from the first characterization of ryegrass staggers to the determination of the toxicokinetics of lolitrem B and of their mechanism of action in mammals, focusing on the different factors that could explain the worldwide distribution of the disease. Other indole diterpene alkaloids than lolitrem B that can be found in Epichloë infected ryegrass, and their tremorgenic properties, are presented in the last section of this review. Full article
Show Figures

Figure 1

Article
The Effect of Co-Administration of Death Camas (Zigadenus spp.) and Low Larkspur (Delphinium spp.) in Cattle
Toxins 2016, 8(1), 21; https://doi.org/10.3390/toxins8010021 - 12 Jan 2016
Cited by 3 | Viewed by 2050
Abstract
In many rangeland settings, there is more than one potential poisonous plant. Two poisonous plants that are often found growing simultaneously in the same location in North American rangelands are death camas (Zigadenus spp.) and low larkspur (Delphinium spp.). The objective [...] Read more.
In many rangeland settings, there is more than one potential poisonous plant. Two poisonous plants that are often found growing simultaneously in the same location in North American rangelands are death camas (Zigadenus spp.) and low larkspur (Delphinium spp.). The objective of this study was to determine if co-administration of death camas would exacerbate the toxicity of low larkspur in cattle. Cattle dosed with 2.0 g of death camas/kg BW showed slight frothing and lethargy, whereas cattle dosed with both death camas and low larkspur showed increased clinical signs of poisoning. Although qualitative differences in clinical signs of intoxication in cattle co-treated with death camas and low larkspur were observed, there were not any significant quantitative differences in heart rate or exercise-induced muscle fatigue. Co-treatment with death camas and low larkspur did not affect the serum zygacine kinetics, however, there was a difference in the larkspur alkaloid kinetics in the co-exposure group. Overall, the results from this study suggest that co-exposure to death camas and low larkspur is not significantly more toxic to cattle than exposure to the plants individually. The results from this study increase our knowledge and understanding regarding the acute toxicity of death camas and low larkspur in cattle. Full article
Show Figures

Figure 1

2015

Jump to: 2020, 2018, 2017, 2016

Article
Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5
Toxins 2016, 8(1), 12; https://doi.org/10.3390/toxins8010012 - 30 Dec 2015
Cited by 6 | Viewed by 2491
Abstract
Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes [...] Read more.
Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes the death of patients, but the pathophysiological mechanisms under these adverse effects are not clear. Here, two solanidine-type VAs (isorubijervine and rubijervine) isolated from Veratrum taliense exhibited strong cardiovascular toxicity. A pathophysiological study indicated that these VAs blocked sodium channels NaV1.3–1.5 and exhibited the strongest ability to inhibit NaV1.5, which is specifically expressed in cardiac tissue and plays an essential role in cardiac physiological function. This result reveals that VAs exert their cardiovascular toxicity via the NaV1.5 channel. The effects of VAs on NaV1.3 and NaV1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively. Full article
Show Figures

Graphical abstract

Review
Toxicosis by Plant Alkaloids in Humans and Animals in Colombia
Toxins 2015, 7(12), 5408-5416; https://doi.org/10.3390/toxins7124892 - 11 Dec 2015
Cited by 17 | Viewed by 3172
Abstract
Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and [...] Read more.
Due to its tropical location, chains of mountains, inter-Andean valleys, Amazon basin area, eastern plains and shores on both the Atlantic and Pacific Oceans, Colombia has many ecosystems and the second largest plant biodiversity in the world. Many plant species, both native and naturalized, are currently recognized as toxic for both animals and humans, and some of them are known to cause their toxic effects due to their alkaloid content. Among these, there are plants containing the hepatotoxic pyrrolizidine alkaloids, neurotoxins such as the indolizidine alkaloid swainsonine and the piperidine alkaloids coniine and γ-coniceine and tropane alkaloids. Unfortunately, the research in toxic plants in Colombia is not nearly proportional to its plant biodiversity and the scientific information available is only very scarce. The present review aims at summarizing the scarce information about plant alkaloid toxicosis in animals and humans in Colombia. Full article
Review
Alkaloid-Containing Plants Poisonous to Cattle and Horses in Europe
Toxins 2015, 7(12), 5301-5307; https://doi.org/10.3390/toxins7124884 - 08 Dec 2015
Cited by 23 | Viewed by 4087
Abstract
Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in [...] Read more.
Alkaloids, nitrogen-containing secondary plant metabolites, are of major interest to veterinary toxicology because of their occurrence in plant species commonly involved in animal poisoning. Based on epidemiological data, the poisoning of cattle and horses by alkaloid-containing plants is a relatively common occurrence in Europe. Poisoning may occur when the plants contaminate hay or silage or when forage alternatives are unavailable. Cattle and horses are particularly at risk of poisoning by Colchicum autumnale (meadow saffron), Conium maculatum (poison hemlock), Datura stramonium (jimson weed), Equisetum palustre (marsh horsetail), Senecio spp. (ragwort and groundsel) and Taxus baccata (European yew). This review of poisonous alkaloid-containing plants describes the distribution of these plants, conditions under which poisoning occurs, active toxic principles involved and subsequent clinical signs observed. Full article
Article
Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala
Toxins 2015, 7(11), 4507-4518; https://doi.org/10.3390/toxins7114507 - 03 Nov 2015
Cited by 21 | Viewed by 2536
Abstract
Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The [...] Read more.
Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 μmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. Full article
Show Figures

Graphical abstract

Back to TopTop