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.

Toxic effect of common poisonous plants of district Bannu, Khyber Pakhtunkhwa, Pakistan.

The present paper was a part of Ph.D research work, conducted during the year 2014, in which 87 poisonous plants belonging to 54 genera, were collected, documented and preserved in the herbarium of Bannu, Department of Botany UST, Bannu Khyber Pakhtunkwa Pakistan. The plants were identified botanically, arranged alphabetically along with their Latin name, family name, common name, poisonous parts, toxicity, affects, toxin and their effects. Aim of the study was to induce awareness in the local people of district Bannu about the poisonous effects of the commonly used plants. Data about poisonous effect were collected from the local experienced and mostly old age people through questionnaire. Some information were collected from a number of veterinary texts and literature. The most important plants genera studied in the area were Brassica 6 species (11.11%), Lathyrus 5 spp (9.26%), Astragalus, Euphorbia and Prunus were with 4 spp (7.40%). Datura, Jatropha, Ranunculus, Solanum and Sorghum were with 3 spp (5.56%) while Allium, Amaranthus, Chenopodium, Melilotus and Taxus were with 2 spp (3.70%). These 15 genera contribute 48 species (55.17 %) while the remaining 39 genera have single species each and contribute 44.83% to the total poisonous flora of the research area. Other important poisonous plants were Anagallis arvensis L., Cannabis sativa, Datura stramonium L., D. metel L., Euphorbia species, Heliotropium europaeum, Ipomoea tricolor, Jatropha curcas, Lolium temulentum L., Malus domestica, Mangifera indica L., Medicago sativa L., Melilotus alba Desr., M. officinalis (L.) Lam., Mirabilis jalapa L., Narcissus tazetta, Nicotiana tabacum L., Sorghum halepense (L) Pers., and Xanthium strumarium. It was concluded that the local population had poor knowledge about the poisonous effect of the plants and the present research work was anticipated for use by health care professionals, veterinarians, farmers, homeowners, as well as botanically curious individuals.

Detection of Pyrrolizidine Alkaloid DNA Adducts in Livers of Cattle Poisoned with Heliotropium europaeum.

Pyrrolizidine alkaloids are among the most common poisonous plants affecting livestock, wildlife, and humans. Exposure of humans and livestock to toxic pyrrolizidine alkaloids through the intake of contaminated food and feed may result in poisoning, leading to devastating epidemics. During February 2014, 73 mixed breed female beef cows from the Galilee region of Israel were accidently fed pyrrolizidine alkaloid contaminated hay for 42 days, resulting in the sudden death of 24 cows over a period of 63 days. The remaining cows were slaughtered 2.5 months after the last ingestion of the contaminated hay. In this study, we report the histopathological analysis of the livers from five of the slaughtered cows and quantitation of pyrrolizidine alkaloid-derived DNA adducts from their livers and three livers of control cows fed with feed free of weeds producing pyrrolizidine alkaloids. Histopathological examination revealed that the five cows suffered from varying degrees of bile duct proliferation, fibrosis, and megalocytosis. Selected reaction monitoring HPLC-ES-MS/MS analysis indicated that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts were formed in all five livers. The livers from the three control cows did not have any liver damage nor any indication of DHP-DNA adduct formed. These results confirm that the toxicity observed in these cattle was caused by pyrrolizidine alkaloid poisoning and that pyrrolizidine alkaloid-derived DNA adducts could still be detected and quantified in the livers of the chronically poisoned cows 2.5 months after their last exposure to the contaminated feed, suggesting that DHP-derived DNA adducts can serve as biomarkers for pyrrolizidine alkaloid exposure and poisoning.

What risks do herbal products pose to the Australian community?

Traditional herbal products are widely used in Australia to treat a broad range of conditions and diseases. It is popularly believed that these products are safer than prescribed drugs. While many may be safe, it is worrying that the specific effects and harmful interactions of a number of their components with prescription medications is not well understood. Some traditional herbal preparations contain heavy metals and toxic chemicals, as well as naturally occurring organic toxins. The effects of these substances can be dire, including acute hepatic and renal failure, exacerbation of pre-existing conditions and diseases, and even death. The content and quality of herbal preparations are not tightly controlled, with some ingredients either not listed or their concentrations recorded inaccurately on websites or labels. Herbal products may also include illegal ingredients, such as ephedra, Asarum europaeum (European wild ginger) and endangered animal species (eg, snow leopard). An additional problem is augmentation with prescription medications to enhance the apparent effectiveness of a preparation. Toxic substances may also be deliberately or inadvertently added: less expensive, more harmful plants may be substituted for more expensive ingredients, and processing may not be adequate. The lack of regulation and monitoring of traditional herbal preparations in Australia and other Western countries means that their contribution to illness and death is unknown. We need to raise awareness of these problems with health care practitioners and with the general public.

Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity.

The aim of the present study is to assess the genotoxicity of Dipterygium glaucum grows widely in Saudi Arabia desert to produce safety herbal products. This work is considered the first and pioneer report so far due to the lack and poor evaluated reports of the plant species for their mutagensity, genotoxicity and cytogenetics effects. Cytogenetic effects of D. glaucum on mitotic in roots of Vicia faba showed reduction in mitotic activity using three extracts; water, ethanol and ethyl acetate. Chromosomal abnormalities were recorded that included stickiness of chromosomes, chromatin bridge, fragments, lagging chromosome and micronuclei. Protein bands and RAPD analyses of V. faba treated with three D. glaucum extracts revealed some newly induced proteins and DNA fragments and other disappeared. Chemical constitution of the plant species should be identified with their biological activities against human and animal cells like HeLa cancer cell line. We are recommending using additional genotoxicity tests and other toxicity tests on animal culture with different concentrations and also utilizing several drought and heat tolerant genes of the plant species in gene cloning to develop and improve other economical crop plants instead of using the species as oral herbal remedy.

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.

Poisoning by Herbs and Plants: Rapid Toxidromic Classification and Diagnosis.

The American Association of Poison Control Centers has continued to report approximately 50,000 telephone calls or 8% of incoming calls annually related to plant exposures, mostly in children. Although the frequency of plant ingestions in children is related to the presence of popular species in households, adolescents may experiment with hallucinogenic plants; and trekkers and foragers may misidentify poisonous plants as edible. Since plant exposures have continued at a constant rate, the objectives of this review were (1) to review the epidemiology of plant poisonings; and (2) to propose a rapid toxidromic classification system for highly toxic plant ingestions for field use by first responders in comparison to current classification systems. Internet search engines were queried to identify and select peer-reviewed articles on plant poisonings using the key words in order to classify plant poisonings into four specific toxidromes: cardiotoxic, neurotoxic, cytotoxic, and gastrointestinal-hepatotoxic. A simple toxidromic classification system of plant poisonings may permit rapid diagnoses of highly toxic versus less toxic and nontoxic plant ingestions both in households and outdoors; direct earlier management of potentially serious poisonings; and reduce costly inpatient evaluations for inconsequential plant ingestions. The current textbook classification schemes for plant poisonings were complex in comparison to the rapid classification system; and were based on chemical nomenclatures and pharmacological effects, and not on clearly presenting toxidromes. Validation of the rapid toxidromic classification system as compared to existing chemical classification systems for plant poisonings will require future adoption and implementation of the toxidromic system by its intended users.

POISONING BY THE SWAINSONINE-CONTAINING PLANT SIDA CARPINIFOLIA IN CAPTIVE SAMBAR DEER (CERVUS UNICOLOR).

Plant intoxications in wildlife are difficult to diagnose, are overlooked, or are sometimes even neglected. Hence, factors that induce wild animals to ingest poisonous plants have not been sufficiently documented. An outbreak of glycoprotein storage disease in sambar deer ( Cervus unicolor ), induced by ingestion of the swainsonine-containing plant, common wireweed (Sida carpinifolia), is reported. Nine out of 55 deer held by a zoo in Brazil were affected. The poisoning was characterized by emaciation and neurologic signs followed by unexpected death in some of the animals. Animals presented abnormal consciousness, posterior paresis, and musculoskeletal weakness; less evident were vestibulo-cerebellar signs. Histologically, there was vacuolation of neurons and epithelial cells of the pancreatic acines, thyroid follicules, and renal tubules. Furthermore, in the central nervous system were axonal degeneration, necrosis, and loss of neurons. Three factors may lead to the ingestion of S. carpinifolia by sambar deer: 1) A grazing field with only S. carpinifolia as a source of forage; 2) a large number of animals kept in this field; and 3) a hierarchy within a cervid group in which dominant males isolated and displaced juvenile and weaker adult males, leaving them with access to only S. carpinifolia.

[Irritant contact dermatitis caused by direct contact with oleander (Nerium oleander)]. / Dermatite irritative par contact direct avec du laurier rose (Nerium oleander).

BACKGROUND: Although the oleander plant is practically ubiquitous throughout the Mediterranean area, very few publications refer to its cutaneous toxicity. PATIENTS AND METHODS: Herein, we report two cases of irritant contact dermatitis caused by oleander. The patients in question were twins who had oleander leaves applied directly to their face for 20minutes. The initial lesions consisted of periorbital erythema, followed by the emergence of papules and macules. Vesicles and crusts appeared over the ensuing 24hours. Treatment included withdrawal of the toxic agent, prescription of oral antihistamines, and the topical application of dermocorticoids to the lesions for two weeks. The outcome on the 9th day was slightly hypochromic and atrophic. Complete restitutio ad integrum of the skin was observed after 30 days. DISCUSSION: In our patients, a joint effect of ultraviolet radiation (phytophotodermatitis) and chlorine from the swimming pool cannot be ruled out. Although the substances present in oleanders (irritant saponins and glycosides) can cause chemical irritant dermatitis, immunological reactions cannot be excluded. The lack of signs of systemic toxicity observed is the result of the factors governing transdermal diffusion of the toxic glycosides found in oleander. CONCLUSION: These two cases provide a timely reminder, both for the general public and for healthcare professionals, of the potential biohazards of oleander, not only because of its systemic toxicity but also because of the risks associated with cutaneous exposure.

Acute death as a result of poisoning tropical (Bos taurus indicus) but not temperate (Bos taurus taurus) cattle after oral dosing with Lupinus leucophyllus (velvet lupine).

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Poisonings in ruminants by Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis (Fabaceae): A mini-review of teratogenic potential and phytochemical evidence.

Teratogenic plants can be found in pastures in different parts of the world and represent a threat to the reproduction of ruminants. In the northeast region of Brazil, several studies have indicated that Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis is one of the main poisonous plants that causes reproductive problems in sheep and goats. In this context, the present study reviewed spontaneous and experimental poisonings reports by C. pyramidale in sheep and goats, as well as analyzing the phytochemical evidence related to this species. The scientific documents were retrieved from different databases and, after applying the selection criteria, a total of 16 articles published between 2000 and 2024 were included in this review. Cenostigma pyramidale causes embryonic loss, abortion, and congenital malformations in pregnant sheep and goats in the Brazilian semi-arid region. The main malformations observed in newborn animals are arthrogryposis, scoliosis, micrognathia, multiple skull deformities, cleft palate, and brachygnathism. Many secondary metabolites have already been isolated from C. pyramidale, however, to date, no evidence has been found regarding the possible teratogenic compounds that occur in this plant. From this perspective, new phytochemical studies are necessary to help unravel the mechanisms of action of embryotoxic agents from C. pyramidale.

Poisonous plants: effects on embryo and fetal development.

Poisonous plant research in the United States began over 100 years ago as a result of livestock losses from toxic plants as settlers migrated westward with their flocks, herds, and families. Major losses were soon associated with poisonous plants, such as locoweeds, selenium accumulating plants, poison-hemlock, larkspurs, Veratrum, lupines, death camas, water hemlock, and others. Identification of plants associated with poisoning, chemistry of the plants, physiological effects, pathology, diagnosis, and prognosis, why animals eat the plants, and grazing management to mitigate losses became the overarching mission of the current Poisonous Plant Research Laboratory. Additionally, spin-off benefits resulting from the animal research have provided novel compounds, new techniques, and animal models to study human health conditions (biomedical research). The Poisonous Plant Research Laboratory has become an international leader of poisonous plant research as evidenced by the recent completion of the ninth International Symposium on Poisonous Plant Research held July 2013 in Hohhot, Inner Mongolia, China. In this article, we review plants that negatively impact embryo/fetal and neonatal growth and development, with emphasis on those plants that cause birth defects. Although this article focuses on the general aspects of selected groups of plants and their effects on the developing offspring, a companion paper in this volume reviews current understanding of the physiological, biochemical, and molecular mechanisms of toxicoses and teratogenesis.

A review of the most economically important poisonous plants to the livestock industry on temperate grasslands of China.

The majority of the literature on poisonous plant species in China is published in Chinese and not available to the majority of interested researchers and grassland managers in other countries. Therefore, a review of the Chinese literature was conducted to summarize the occurrence of poisonous plant species on temperate grasslands in China. We reviewed the literature to obtain general information on poisonous species but focus on locoweeds (Astragalus and Oxytropis spp.), drunken horse grass [Achnatherum inebrians (Hance) Keng ex Tzvelev] and langdu (Stellera chamaejasme L.) for information on their toxins, distribution and ecology, control methods and alternate uses. Of the almost 1300 poisonous species found on grasslands in China, these species are responsible for an estimated 80% of all livestock losses. This includes loss of performance as well as mortality. The locoweeds are a complex made up of Oxytropis and Astragalus species. The toxic principle in this complex, as well as in drunken horse grass, is the result of an endophyte fungus whereas in langdu it is produced by the plant. All these species are native to the grasslands, which suggest they have been a problem ever since herding began. Over that period of at least several millennia, herders would have learned and adapted to the presence of poisonous species. Strategies were developed and therapies employed to allow the animals to cope before and after poisoning. Nevertheless, grazing management could still be refined that would allow the use of the toxic legumes, while preventing poisonous symptoms, as has been tested elsewhere.

A review of oxalate poisoning in domestic animals: tolerance and performance aspects.

Published data on oxalate poisoning in domestic animals are reviewed, with a focus on tolerance and performance. Oxalic acid is one of a number of anti-nutrients found in forage. It can bind with dietary calcium (Ca) or magnesium (Mg) to form insoluble Ca or Mg oxalate, which then may lead to low serum Ca or Mg levels as well as to renal failure because of precipitation of these salts in the kidneys. Dietary oxalate plays an important role in the formation of Ca oxalate, and a high dietary intake of Ca may decrease oxalate absorption and its subsequent urinary excretion. Oxalate-rich plants can be supplemented with other plants as forage for domestic animals, which may help to reduce the overall intake of oxalate-rich plants. Non-ruminants appear to be more sensitive to oxalate than ruminants because in the latter, rumen bacteria help to degrade oxalate. If ruminants are slowly exposed to a diet high in oxalate, the population of oxalate-degrading bacteria in the rumen increases sufficiently to prevent oxalate poisoning. However, if large quantities of oxalate-rich plants are eaten, the rumen is overwhelmed and unable to metabolize the oxalate and oxalate-poisoning results. Based on published data, we consider that <2.0% soluble oxalate would be an appropriate level to avoid oxalate poisoning in ruminants, although blood Ca level may decrease. In the case of non-ruminants, <0.5% soluble oxalate may be acceptable. However, these proposed safe levels of soluble oxalate should be regarded as preliminary. Further studies, especially long-term studies, are needed to validate and improve the recommended safe levels in animals. This review will encourage further research on the relationships between dietary oxalate, other dietary factors and renal failure in domestic animals.

A single point mutation in ricin A-chain increases toxin degradation and inhibits EDEM1-dependent ER retrotranslocation.

Ricin is a potent plant cytotoxin composed of an A-chain [RTA (ricin A-chain)] connected by a disulfide bond to a cell binding lectin B-chain [RTB (ricin B-chain)]. After endocytic uptake, the toxin is transported retrogradely to the ER (endoplasmic reticulum) from where enzymatically active RTA is translocated to the cytosol. This transport is promoted by the EDEM1 (ER degradation-enhancing α-mannosidase I-like protein 1), which is also responsible for directing aberrant proteins for ERAD (ER-associated protein degradation). RTA contains a 12-residue hydrophobic C-terminal region that becomes exposed after reduction of ricin in the ER. This region, especially Pro250, plays a crucial role in ricin cytotoxicity. In the present study, we introduced a point mutation [P250A (substitution of Pro250 with alanine)] in the hydrophobic region of RTA to study the intracellular transport of the modified toxin. The introduced mutation alters the secondary structure of RTA into a more helical structure. Mutation P250A increases endosomal-lysosomal degradation of the toxin, as well as reducing its transport from the ER to the cytosol. Transport of modified RTA to the cytosol, in contrast to wild-type RTA, appears to be EDEM1-independent. Importantly, the interaction between EDEM1 and RTA(P250A) is reduced. This is the first reported evidence that EDEM1 protein recognition might be determined by the structure of the ERAD substrate.

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.

Genus identification of toxic plant by real-time PCR.

Some plants have toxicities that are dangerous for humans. In the case of poisoning by toxic plants, a rapid and easy screening test is required for accurate medical treatment or forensic investigation. In this study, we designed specific primer pairs for identification of toxic plants, such as subgenus Aconitum, genus Ricinus, genus Illicium, and genus Scopolia, by internal transcribed spacer sequences of nuclear ribosomal DNA. Allied species of target plants, foods, and human DNA were not detected, but each primer pair provided a specific PCR product from the target plant using real-time PCR. This method can detect the subgenus Aconitum, genus Ricinus, and genus Scopolia with template DNA of 10 pg, respectively, and genus Illicium with 1 pg. Furthermore, each primer pair provided the exact PCR product from digested target plants in artificial gastric fluid. When a trace unknown plant sample in forensic investigation is collected from stomach contents, this PCR assay may be useful for screening toxic plants.

A toxicokinetic comparison of norditerpenoid alkaloids from Delphinium barbeyi and D. glaucescens in cattle.

Cattle are poisoned by N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and 7,8-methylenedioxylycoctonine type (MDL-type) norditerpenoid alkaloids in Delphinium spp. Alkaloids in D. glaucescens are primarily of the MSAL-type, while D. barbeyi is a mixture of MSAL and MDL-types. The objectives of this study were to determine and compare the toxicokinetics of selected alkaloids from D. glaucescens and D. barbeyi in cattle. The two species of larkspur were dosed to three groups of Angus steers via oral gavage at doses of 8 mg kg⁻¹ MSAL-type alkaloids for D. barbeyi and either 8.0 or 17.0 mg kg⁻¹ MSAL-type alkaloids for D. glaucescens. In cattle dosed with D. barbeyi, serum deltaline (MDL-type) concentrations peaked at 488 ± 272 ng ml⁻¹ at 3 h and serum methyllycaconitine (MSAL-type) concentrations peaked at 831 ± 369 ng ml⁻¹ at 6 h. Deltaline was not detected in the serum of cattle dosed with D. glaucescens. Serum methyllycaconitine concentrations peaked at 497 ± 164 ng ml⁻¹ at 18 h, and 1089 ± 649 ng ml⁻¹ at 24 h for the 8 mg kg⁻¹ and 17 mg kg⁻¹ doses of D. glaucescens respectively. There were significant differences between the maximum serum concentrations and the area under the curve for the two doses of D. glaucescens but not D. barbeyi. Results from this experiment support the recommendation that approximately 7 days are required to clear 99% of the toxic alkaloids from the serum of animals orally dosed with D. barbeyi or D. glaucescens, and that MDL-type alkaloids play an important role in the toxicity of Delphinium spp. in cattle.

Mechanism of action of stinging nettles.

OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called "stinging nettles" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted.