Search Results (64)

Pyrrolizidine alkaloids are plant-derived toxins with environmental persistence and the potential to contaminate soil, water, and adjacent crops. This study investigated the leaching behavior and environmental fate of PAs from two PA-producing weeds—Myosotis arvensis L. (Boraginaceae) and Senecio vulgaris L. (Asteraceae)—in two Latvian agricultural soils: sandy loam and loam. Hot- and cold-water plant extracts were applied to soil columns (10 cm and 20 cm), and leachates were analyzed over a 14-day period using QuEChERS purification and LC-HRMS detection. Leaching varied by plant species, extract type, and soil. M. arvensis showed significantly higher cumulative leaching (77–84% for cold, 65–71% for hot extracts), attributed to the higher solubility of N-oxides. In contrast, S. vulgaris extracts leached minimally (<0.84% from sandy loam) and were undetectable in loam. The presence of cyclic diester PAs in S. vulgaris and the higher cation exchange capacity of loam favored retention or degradation. PANO-to-PA conversion occurred in both soils, indicating redox activity. The fate of PAs was influenced by structural type (diesters showing higher persistence), extraction method (hot extraction releasing more pyrrolizidine alkaloids), and soil properties such as pH, organic matter, and cation exchange capacity, which affected sorption and mobility. These findings underscore the significance of soil composition in controlling PA mobility and associated environmental risks. Future research should focus on long-term PA persistence across diverse soil types and investigate crop uptake potential and microbial degradation pathways under field conditions. Full article

Pyrrolizidine alkaloids (PAs) are a class of nitrogen-containing basic organic compounds that are frequently detected in foods and herbal medicines. Owing to their potential hepatotoxic, genotoxic, and carcinogenic properties, PAs have become a significant focus for monitoring global food safety. In this study, an ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was developed for the detection and analysis of three foods (tea, honey, and milk) susceptible to PA contamination. This optimized method effectively separated and detected three types of PAs, namely, three pairs of isomers and two pairs of chiral compounds. The limits of detection (LODs) and limits of quantification (LOQs) were determined to be 0.015–0.75 and 0.05–2.5 µg/kg, respectively, with the relative standard deviations (RSDs) of both the interday and intraday precisions remaining below 15%. The average PA recoveries from the honey, milk, and tea matrices fell within the ranges of 64.5–103.4, 65.2–112.2, and 67.6–107.6%, respectively. This method was also applied to 77 samples collected from 33 prefecture-level cities across 16 provinces and included 40 tea, 6 milk, 8 honey, 14 spice, and 9 herbal medicine samples. At least one PA was detected in twenty-three of the samples, with herbal medicines exhibiting the highest total PA content. The obtained results indicate that the developed method demonstrated good repeatability and stability in the detection and quantitative analyses of PAs in food- and plant-derived samples. This method is therefore expected to provide reliable technical support for food safety risk monitoring. Full article

Pyrrolizidine alkaloids (PAs) are common phytotoxins that are found worldwide. Upon hepatic metabolic activation, the reactive PA metabolites covalently bind to DNAs and form DNA adducts, causing mutagenicity and tumorigenicity in the liver. However, the molecular basis of the formation and removal of PA-derived DNA adducts remains largely unexplored. In the present study, Sprague Dawley (SD) rats were exposed to retrorsine (RTS), a representative PA, at a human-relevant dose of 3.3 mg/kg/day for 28 days. The rats were divided into three groups: control, RTS-28 (sacrificed after continuous RTS exposure), and RTS-161 (sacrificed at 133 days post-RTS-exposure). The multi-omics analyses demonstrated the involvement of homologous recombination (HR) and non-homologous end joining (NHEJ) repair pathways as a response to PA-induced DNA damage. Additionally, the characteristic guanine adducts induced by RTS exposure were in accordance with the higher expression of XPA and XPC, indicating that nucleotide excision repair (NER) and base excision repair (BER) also contributed to repairing RTS-induced DNA damage. Furthermore, we also showed that DNA damage persisted after PA exposure, and mutagenically related repair errors might occur due to the prolonged genotoxic effects. The present study lays the foundation for bridging PA-derived DNA adducts, DNA damage, DNA repair, and the follow-up mutagenesis and carcinogenesis associated with PA exposure. Full article

One of the challenges of the pharmaceutical and cosmetic industries is to deliver biochemical compounds that can be advantageous for the skin. Research on Boraginaceae taxa has confirmed their use in traditional medicine and proved the potential biological importance of various molecules in cosmetology. The main classes of valuable compounds associated with Boraginaceae taxa are fatty acids, including γ-linolenic acid, essential oils, phenolic acids (e.g., rosmarinic acid), flavonoids, anthocyanins, tannins, and saponins. Highly specific are naphthoquinone pigments (including shikonin) and allantoin. Another distinguishing feature is the accumulation of silica (silicon dioxide) in trichomes. Some taxa produce mucilages. However, pyrrolizidine alkaloids (PAs) with toxic properties are also found (mainly in Symphytum spp.); therefore, their applications should be avoided. Extracts or individual compounds of Boraginaceae plants are characterized by antioxidant, anti-inflammatory, antiseptic, anti-irritant, antiaging, and photoprotective activities. Boraginaceae products are widespread in the cosmetic industry as ingredients of creams, balms, lotions, gels, shampoos, lipsticks, perfumes, and deodorants. The most valuable for the cosmetic industry are raw materials obtained from the genera Alcanna Anchusa, Arnebia, Borago, Buglossoides, Cerinthe, Cordia, Echium, Ehretia, Eriodictyon, Glendora, Lappula, Lithospermum, Lycopsis, Macrotomia, Maharanga, Mertensia, Messerschmidia, Myosotis, Omphalodes, Onosma, Pulmonaria, Rindera, Symphytum, Trachystemon, and Trigonotis. Further research should focus on the search for active substances in other plants of the family. Full article

Invasive plant species pose a significant threat to global biodiversity and ecosystems. Climate changes favor the spread of non-native plants, whether voluntary or accidentally introduced into a new environment, as these plants possess a greater ability to adapt to changing environments. The spreading of these alien species has a negative impact also on agro-ecosystems, on agricultural yields, and on the nutritional quality of food crops. The high metabolic plasticity of these plants helps them to adapt to new ecosystems, enabling them to succeed in competing with crops. In particular, many alien plants are producers of alkaloids. These molecules represent the main chemical defense to biotic stressors and also the major risk for human health. In this review, we focused on invasive plants producing tropane alkaloids (TAs) and pyrrolizidine alkaloids (PAs). We explored the potential role of these molecules in the fitness of invasive plants in the context of climate change and reviewed the knowledge regarding their biosynthesis steps and examined the mechanism of toxicity when accidentally ingested. Finally, we summarized the most efficient analytical and molecular methods to detect either alkaloid contamination or the presence of invasive plant contaminants, which are the source of these molecules, in food crops. Possible solutions and precautions to ensure food safety have been also proposed. Full article

Pyrrolizidine alkaloids (PAs) are toxic compounds that occur naturally in certain plants, however, there are many secondary pathways causing PA contamination of other plants, including medicinal herbs and plant-based food products, which pose a risk of human intoxication. It is proven that chronic exposure to PAs causes serious adverse health consequences resulting from their cytotoxicity and genotoxicity. This review briefly presents PA occurrence, structures, chemistry, and toxicity, as well as a set of analytical methods. Recently developed sensitive electrochemical and chromatographic methods for the determination of PAs in honey, teas, herbs, and spices were summarized. The main strategies for improving the analytical efficiency of PA determination are related to the use of mass spectrometric (MS) detection; therefore, this review focuses on advances in MS-based methods. Raising awareness of the potential health risks associated with the presence of PAs in food and herbal medicines requires ongoing research in this area, including the development of sensitive methods for PA determination and rigorous legal regulations of PA intake from herbal products. The maximum levels of PAs in certain products are regulated by the European Commission; however, the precise knowledge about which products contain trace but significant amounts of these alkaloids is still insufficient. Full article

A miniaturized solid-phase extraction of two tropane alkaloids (TAs) and twenty-one pyrrolizidine alkaloids (PAs) from infusions of dry edible flowers using optimized µSPEed^® technique was developed. The optimization of the µSPEed^® methodology involved testing different cartridges and comparing various volumes and numbers of loading cycles. The final conditions allowed for a rapid extraction, taking only 3.5 min. This was achieved using a C18-ODS cartridge, conditioning with 100 µL of methanol (two cycles), loading 100 µL of the infusion sample (seven cycles), and eluting the analytes with 100 µL of methanol (two cycles). Prior to their analysis by UHPLC-IT-MS/MS, the extracts were evaporated and reconstituted in 100 µL of water (0.2% formic acid)/methanol (0.2% ammonia) 95:5 (v/v), allowing for a preconcentration factor of seven times. The methodology was successfully validated obtaining recoveries ranging between 87 and 97%, RSD of less than 12%, and MQL between 0.09 and 0.2 µg/L. The validated methodology was applied to twenty samples of edible flower infusions to evaluate the safety of these products. Two infusion samples obtained from Acmella oleracea and Viola tricolor were contaminated with 0.16 and 0.2 µg/L of scopolamine (TA), respectively, while the infusion of Citrus aurantium was contaminated with intermedine and lycopsamine (PAs) below the MQL. Full article

Pyrrolizidine alkaloids (PAs) are naturally occurring secondary metabolites of plants. To date, more than 660 types of PAs have been identified from an estimated 6000 plants, and approximately 120 of these PAs are hepatotoxic. As a result of PAs being found in spices, herbal teas, honey, and milk, PAs are considered contaminants in foods, posing a potential risk to human health. Here, we summarize the chemical structure, toxic effects, levels, and regulation of PAs in different countries to provide a better understanding of their toxicity and risk assessment. With recent research on the risk assessment of PAs, this review also discusses the challenges facing this field, aiming to provide a scientific basis for PA toxicity research and safety assessment. Full article

Consumers are increasingly seeking natural alternatives to chemical compounds, including the use of dried aromatic plants as seasonings instead of salt. However, the presence of pyrrolizidine alkaloids (PAs) in food supplements and dried plants has become a concern because of their link to liver diseases and their classification as carcinogenic by the International Agency for Research on Cancer (IARC). Despite European Union (EU) Regulation (EU) 2023/915, non-compliance issues persist, as indicated by alerts on the Rapid Alert System for Food and Feed (RASFF) portal. Analyzing PAs poses a challenge because of their diverse chemical structures and low concentrations in these products, necessitating highly sensitive analytical methods. Despite these challenges, ongoing advancements in analytical techniques coupled with effective sampling and extraction strategies offer the potential to enhance safety measures. These developments aim to minimize consumer exposure to PAs and safeguard their health while addressing the growing demand for natural alternatives in the marketplace. Full article

Stingless bee honeys (SBHs) from Australian and Malaysian species were analysed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the presence of pyrrolizidine alkaloids (PAs) and the corresponding N-oxides (PANOs) due to the potential for such hepatotoxic alkaloids to contaminate honey as a result of bees foraging on plants containing these alkaloids. Low levels of alkaloids were found in these SBHs when assessed against certified PA standards in targeted analysis. However, certain isomers were identified using untargeted analysis in a subset of honeys of Heterotrigona itama which resulted in the identification of a PA weed species (Ageratum conyzoides) near the hives. The evaluation of this weed provided a PA profile matching that of the SBH of H. itama produced nearby, and included supinine, supinine N-oxide (or isomers) and acetylated derivatives. These PAs lacking a hydroxyl group at C7 are thought to be less hepatoxic. However, high levels were also observed in SBH (and in A. conyzoides) of a potentially more toxic diester PA corresponding to an echimidine isomer. Intermedine, the C7 hydroxy equivalent of supinine, was also observed. Species differences in nectar collection were evident as the same alkaloids were not identified in SBH of G. thoracica from the same location. This study highlights that not all PAs and PANOs are identified using available standards in targeted analyses and confirms the need for producers of all types of honey to be aware of nearby potential PA sources, particularly weeds. Full article

Pyrrolizidine alkaloids (PAs) are one of the largest distributed classes of toxins in nature. They have a wide range of toxicity, such as hepatotoxicity, pulmonary toxicity, neuronal toxicity, and carcinogenesis. Yet, biological targets responsible for these effects are not well addressed. Using methods of computational biology for target identification, we tested more than 200 PAs. We used a machine-learning approach that applies structural similarity for target identification, ChemMapper, and SwissTargetPrediction. The predicted targets with high probabilities were muscarinic acetylcholine receptor M1. The predicted interactions between these two targets and PAs were further studied by molecular docking-based binding energies using AutoDock and VinaLC, which revealed good binding affinities. The PAs are bound to the same binding pocket as pirenzepine, a known M1 antagonist. These results were confirmed by in vitro assays showing that PAs increased the levels of intracellular calcium. We conclude that PAs are potential acetylcholine receptor M1 antagonists. This elucidates for the first time the serious neuro-oncological toxicities exerted by PA consumption. Full article

Heterocyclic organic compounds named pyrrolizidine alkaloids (PAs) belong to a group of alkaloids and are synthesized by either plants or microorganisms. Therefore, they are naturally occurring secondary metabolites. They are found in species applied in the pharmaceutical and food industries, thus a thorough knowledge of their pharmacological properties and toxicology to humans is of great importance for their further safe employment. This review is original because it synthesizes knowledge of plant and microbial PAs, which is unusual in the scientific literature. We have focused on the Boraginaceae family, which is unique due to the exceptional richness and diversity of its PAs in plant species. We have also presented the microbial sources of PAs, both from fungi and bacteria. The structure and metabolism of PAs have been discussed. Our main aim was to summarize the effects of PAs on humans, including both negative, toxic ones, mainly concerning hepatotoxicity and carcinogenicity, as well as potentially positive ones for pharmacological and medical applications. We have collected the results of studies on the anticancer activity of PAs from plant and microbial sources (mainly Streptomyces strains) and on the antimicrobial activity of PAs on different strains of microorganisms (bacteria and fungi). Finally, we have suggested potential applications and future perspectives. Full article

Background: Plant-derived pyrrolizidine alkaloids (PAs) in feed cause metabolic disturbances in farm animals resulting in high economic losses worldwide. The molecular pathways affected by these PAs in cells and tissues are not yet fully understood. The objective of the study was to examine the dose-dependent effects of orally applied PAs derived from tansy ragwort in midlactation dairy cows. Methods: Twenty Holstein dairy cows were treated with target exposures of 0, 0.47, 0.95 and 1.91 mg of total PA/kg of body weight/d in control, PA1, PA2 and PA3, respectively, for 28 days. Liver tissue biopsy and plasma and milk samples were taken at day 28 of treatment to assess changes in metabolic pathways. A targeted metabolomics approach was performed to detect the metabolite profiles in all compartments. Results: The PA-affected metabolite profiling in liver tissue, plasma and milk revealed changes in three substrate classes: acylcarnitines (ACs), phosphatidylcholines (PCs) and sphingomyelins (SMs). In addition, in the plasma, amino acid concentrations were affected by PA exposure. Conclusions: PA exposure disturbed liver metabolism at many sites, especially devastating pathways related to energy metabolism and to amino acid utilization, most likely based on mitochondrial oxidative stress. The effects on the milk metabolite profile may have consequences for milk quality. Full article

Pyrrolizidine alkaloids are secondary metabolites produced by plants as a defense against insects. These can cause acute or chronic toxicity in humans. Therefore, avoiding potential poisoning from the consumption of tea and culinary plants contaminated with pyrrolizidine alkaloids (PAs), pyrrolizidine alkaloids N-oxides (PANOs), and tropane alkaloids (TAs) is important for human health and food safety. Therefore, it is important to determine the levels of these substances with reliable and highly accurate methods. In this study, the PAs, PANOs, and TAs in herbal teas and culinary herbs sold in Turkish markets were identified and their levels were determined. Thus, the general profiles of herbal teas and culinary herbs in Turkey were revealed, and the compliance of the total amounts of PA and TA with the regulations was examined. The identification and quantification of 25 PAs and N-oxides and 2 TAs (atropine and scopolamine) in the samples was performed with a liquid chromatography-quadrupole time-of-flight tandem mass spectrometer (LC-Q-ToF/MS). At least a few of these substances were detected in all of the tested herbal teas and culinary herbs. The total contents of the black tea, green tea, mixed tea, flavored tea, chamomile tea, sage tea, linden tea, fennel tea, rosehip tea, peppermint, and thyme samples ranged from 4.6 ng g⁻¹ to 1054.5 ng g⁻¹. The results obtained shed light on the importance of analyzing the total dehydro PA, PANO, and TA amounts in plant-based products consumed in diets with sensitive and accurate methods, and they highlight the necessity of performing these analyses routinely in terms of food safety. Full article