Toxic Alkaloids Research Articles

Detection of tropane alkaloid contaminations in unprocessed soybeans and their fate in food and feed processing

Datura stramonium and other nightshade plants commonly occur as weeds and have the potential to contaminate crops with toxic tropane alkaloids. Here, the contamination of soybeans with the tropane alkaloids atropine and scopolamine after co-harvesting with thornapple plants is reported. The potential route of contamination was found to be independent of the thornapple seeds. The further fate of tropane alkaloids in downstream processes was evaluated in laboratory-scale tofu and soybean oil production. It was determined that a relatively small portion of the alkaloids is persistent in the tofu, while the reduction in soybean oil and press cake is less pronounced. No regulation is in place for the maximum amount of tropane alkaloids in soybeans, but the limits for other food crops were exceeded both in the raw and processed goods.

Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication. Solasodine (SS), a toxic alkaloid from the Solanaceae family, was chosen as the model compound. Complexation was studied using nuclear magnetic resonance (NMR) spectroscopy, molecular modelling, and isothermal titration calorimetry (ITC). NMR in various D2O/DMSO‑d6 media revealed a particularly stable inclusion-type complex, identifying a slow exchange process between the CD and the aminosteroid along with a less significant fast exchange between DMSO and SGM. Using various NMR techniques, the structure and kinetic/thermodynamic parameters of the inclusion complex were explored. Theoretical calculations showed the secondary amino head of SS near the carboxylate ends of the SGM sidechains, facilitating intermolecular ionic interactions. ITC experiments in an aqueous environment provided Ka stability constants of 7.03 × 106 M−1 and 4.17 × 106 M−1 at 25 °C and 37 °C, respectively, similar to previously reported SGM complexes with aminosteroid neuromuscular blockers. Finally, SGM significantly increased cell survival and reduced SS toxicity in mHippoE-14 mouse hippocampal embryonic cells, supporting the hypothesis that SGM could act as an antidote to SS's toxic effects.

Biological damage of monocrotaline on the brain and intestinal tissues of Apis mellifera

Monocrotaline (MCT) is a toxic alkaloid present in plants, posing a threat to animals in terrestrial ecosystems. However, little is known about its potential impacts on pollinating insects. Here, we report the effects of of MCT on the brains and intestines of foraging honeybees (Apis mellifera). MCT exposure resulted in a reduction in head weight and swelling of the abdomen in honeybees. Additionally, MCT exposure caused morphological damage to the brain, characterized by decreased antioxidant capacity and increased apoptosis, along with intestinal tissue damage that was accompanied by increased antioxidant capacity and apoptosis. Moreover, MCT altered the core gut microbial community structure in honeybees and increased the expression of antimicrobial peptide (AMP) genes in the midgut. These findings indicate that exposure to MCT activates the immune response in the honeybee gut, while the brain does not exhibit an immune response but instead experiences oxidative stress. This study provides a resource for future research exploring interactions between MCT and other insects, and can help deepen our understanding of MCT's potential impacts in ecosystems.

Effect of Vernonia Cinerea Water Extract on the Protection of Liver Tissue in Chronic Nicotine-Treated Rats

Nicotine, a highly toxic alkaloid found in tobacco, is known for its addictive properties and systemic side effects, including carcinogenic potential and multi-organ damage. Recent evidence indicates that nicotine can significantly impair liver function and regeneration by promoting fibrogenesis and oxidative stress. This study aimed to investigate the protective effects of Vernonia cinerea (VC) against nicotine-induced liver damage in Wistar rats, focusing on inflammation and pro-fibrosis markers. Thirty male Wistar rats were divided into three groups: a control group, a nicotine group (1 mg/kg/day), and a nicotine plus VC group (1 mg/kg/day nicotine and 100 mg/kg/day VC). Liver tissues were examined using Hematoxylin and Eosin staining, and Masson's trichrome staining to evaluate histological changes. Kupffer cell counts were determined using a Panoramic digital slide scanner. Statistical analyses were conducted to compare the groups. Nicotine exposure led to significant liver damage, characterized by increased inflammation, collagen deposition, and disruption of liver architecture. VC supplementation ameliorated these effects, reducing inflammation and fibrosis markers. Kupffer cell counts were lower in the nicotine plus VC group compared to the nicotine group alone. Conclusion: VC demonstrates a protective role in mitigating nicotine-induced liver damage, highlighting its potential as a therapeutic agent for preventing liver fibrosis and maintaining liver health in nicotine-exposed individuals.

Damage to the behavior and physiological functions of Apis mellifera (Hymenoptera: Apidae) by monocrotaline via the modulation of tryptophan metabolism and the corazonin receptor

Monocrotaline (MCT) is a toxic pyrrolizidine alkaloid found in plants of the Crotalaria genus. As primary pollinators of Crotalaria plants, honeybees come into contact with this harmful substance. However, limited research has been conducted on the effects of MCT on Apis mellifera, particularly the risks of long-term exposure to sublethal concentrations. Through evaluating the proboscis extension reflex (PER) ability, analyzing the honeybee brain transcriptome, and analyzing the honeybee hemolymph metabolome, we discovered that sublethal concentrations of MCT impair the olfactory and memory capabilities of honeybees by affecting tryptophan (Trp) metabolism. Furthermore, MCT upregulates the expression of the corazonin receptor (CrzR) gene in the honeybee brain, which elevates reactive oxygen species (ROS) levels in the brain while reducing glucose levels in the hemolymph, consequently shortening the honeybees' lifespan. Our findings regarding the multifaceted impact of MCT on honeybees lay the foundation for exploring its toxicological pathways and management in honeybee populations.

Exploring the wound healing potential of Lobostemon fruticosus using in vitro and in vivo bioassays

Ethnopharmacological relevanceLobostemon fruticosus (L.) H.Buek is a perennial and woody shrub of the Boraginaceae family, found in the Cape region of South Africa. The leaves and twigs are used to treat dermatological conditions such as wounds, burns, ringworm, erysipelas and eczema. Anti-inflammatory, antibacterial, antiviral and anti-proliferative activities of L. fruticosus have been reported. However, there is a void in research which reports on the wound healing properties of this plant. Aim of the studyAligned with the traditional use of L. fruticosus, our study aimed to use in vitro and in vivo bioassays to confirm the wound healing potential of the plant. Materials and methodsAn aqueous methanol extract (80% v/v) of L. fruticosus was prepared using a sample collected from the Western Cape Province of South Africa and chromatographically profiled by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay was performed to determine the non-toxic concentrations of the extract for subsequent use in the in vitro scratch assay. Both the human keratinocyte (HaCaT) and fibroblast (BJ-5ta) cell lines were employed in the in vitro scratch assay. The in vivo caudal fin amputation assay was used to assess the wound healing potential of L. fruticosus, by monitoring fin regeneration in zebrafish larvae treated with the plant extract at various concentrations. ResultsSix major compounds were tentatively identified in the L. fruticosus extract namely; globoidnan A, globoidnan B, rutin, rabdosiin, sagerinic acid and rosmarinic acid. The potentially toxic pyrrolizidine alkaloids were also identified and quantitatively confirmed to be present at a low concentration of 119.58 ppm (m/m). Treatment of HaCaT and BJ-5ta cells with the plant extract in the scratch assay resulted in an increase in cell migration, which translates to accelerated wound closure. After 24 hr treatment with 100 μg/mL of extract, wound closure was recorded to be 91.1 ± 5.7% and 94.1 ± 1.3% for the HaCaT and BJ-5ta cells, respectively, while the untreated (medium) controls showed 72.3 ± 3.3% and 73.0 ± 4.3% for the two cell lines, respectively. Complete wound closure was observed between 24 and 36 hr, while the untreated control group did not achieve 100% wound closure by the end of the observation period (48 hr). In vivo, the crude extract at 100 μg/mL accelerated zebrafish caudal fin regeneration achieving 100.5 ± 3.8% regeneration compared to 68.3 ± 6.6% in the untreated control at two days post amputation. ConclusionsThe study affirms the wound healing properties, as well as low toxicity of L. fruticosus using both in vitro and in vivo assays, which supports the traditional medicinal use. Other in vitro assays that target different mechanisms involved in wound healing should be investigated to support the current findings.

UHPLC-PDA-ELSD-MS-based simultaneous determination of diterpenoid alkaloids in commercially important Himalayan medicinal plant Aconitum heterophyllum Wall. and network pharmacology-based target prediction

Aconitum heterophyllum Wall., a commercially important Himalayan medicinal plant, is used in various herbal formulations and has high market demand. Given its esteemed medicinal properties, considerable demand, and prioritized status, there’s a pressing requirement for thorough quality assessment methods to ensure high throughput. Genus Aconitum is also well known for its toxicity owing to the presence of diester diterpenoid alkaloids. Hence it is essential to develop a UHPLC-PDA-ELSD-MS based quantification method enabling simultaneous quantification of primary marker compounds alongside toxic diterpenoid alkaloids. The method showcased strong linearity, with detection and quantification limits covering a broad range. Precision was evident with consistently low relative standard deviations both within and across days. Furthermore, accuracy was demonstrated within acceptable bounds. Quantification results revealed the maximum content of atisinium and hetisine in hydroethanolic root extract [atisinium (≅78.88 mg/g) and hetisine (≅50.17 mg/g)] In addition, a network pharmacology-based approach has been applied to predict potential biological targets. The network pharmacology approach suggests the plant’s potential in treating neuralgia, renal fibrosis, diabetes mellitus, lung diseases, cancer, and more, emphasizing the need for scientific validation and indicating future research directions. Overall, the developed method represents a reliable and efficient quality assessment method for the simultaneous quantification of marker compounds and toxic diterpenoid alkaloids in the roots of A. heterophyllum. Network pharmacology predicts pharmacological potentials that require scientific validation highlighting future scope.

Comparison of the acute toxicity of zygacine versus zygadenine

Foothill death camas (Zigadenus paniculatus) is a common poisonous plant found throughout western North America. The toxic alkaloids in foothill death camas are zygadenine, esters of zygadenine, with zygacine, the 3-acetyl ester of zygadenine, often being the most abundant. Two additional esters of zygadenine that are found primarily in the floral parts of foothill death camas are 3-angeloylzygadenine and 3-veratroylzygadeine. Recent research has shown that very little zygacine is detected in the blood of animals dosed with zygacine. A recent investigation into the metabolism of zygacine demonstrated that zygacine is rapidly metabolized to zygadenine, demonstrating a clear first pass effect. The objective of this study was to determine if there is a difference in the acute toxicity of zygacine and zygadenine to mice and sheep. Additionally, two other esters of zygadenine, 3-angeloylzygadenine and 3-veratroylzygadenine, were evaluated for their acute toxicity in a mouse IV LD50 assay. All three esters of zygadenine tested were more toxic than zygadenine, with the following rank order of toxicity in the mouse IV LD50 assay: zygadenine-HCl (59.5 mg/kg) < zygacine-HCl (1.6 mg/kg) < angeloylzygadenine-HCl (1.0 mg/kg) < veratroylzygadenine-HCl (0.5 mg/kg). Similar to the results of the mouse experiments, zygacine-HCl was significantly more toxic than zygadenine-HCl in sheep dosed IV with pure compounds. Sheep dosed with 1.25 mg/kg zygacine-HCl showed severe clinical signs of poisoning. Whereas a dose of 12.5 mg/kg zygadenine-HCl was required to elicit a similar onset and severity of clinical signs. Overall, these data indicate that zygacine is more toxic than zygadenine when administered IV, when first pass metabolism is bypassed.

The Bitter Truth: How Insects Cope with Toxic Plant Alkaloids.

Plants are unique organisms that have developed ingenious strategies to cope with environmental challenges, such as herbivorous insects. One of these strategies is the synthesis of a vast array of chemical compounds, known as specialized metabolites, that serve many ecological functions. Among the most fascinating and diverse groups of specialized metabolites are the alkaloids, which are characterized by the presence of a nitrogen atom within a heterocyclic ring. While some have medicinal and recreational applications, others are highly unpalatable and/or toxic. The effects of alkaloids on both humans and insects can be very diverse, affecting their physiology and behavior. Insects that feed on alkaloid-containing plants have evolved diverse mechanisms to cope with the consequences of these toxins. These include sequestration, where insects store alkaloids in specialized tissues or organs, enzymatic detoxification through enzymes such as cytochrome P450 monooxygenases and glutathione S-transferases, and behavioral adaptations such as selective feeding. In this review, we explore the relationships between plant alkaloids and the evolutionary adaptations that enable insects to exploit alkaloid-rich plants as food sources and ecological niches minimizing the harmful effects of these natural compounds. We aim to provide a comprehensive and updated overview of this fascinating and complex ecological interaction.

Symphytum genus—from traditional medicine to modern uses: an update on phytochemistry, pharmacological activity, and safety

AbstractWith around 34 recognized species, Symphytum genus (comfrey) has a noteworthy position within the Boraginaceae family. Comfrey species have been empirically used since ancient times as wound-healing and skin-regenerating agents in ulcers, wounds, bone fractures, and rheumatic complaints. This review aims to provide a thorough examination of recent scientific advances and challenges within the Symphytum genus, covering data published between 2013 and 2023. It delivers an updated overview of the taxonomy, ethnopharmacological uses, chemical composition, and pharmacological activities of the genus. Special emphasis is put on molecular identification methods for species taxonomy, emerging extraction technologies for comfrey phytochemicals, metabolomics techniques for mapping chemical complexity, modern bioassay platforms revealing its poly-pharmacology, formulation strategies, and remediation approaches for removal of toxic pyrrolizidine alkaloids (PAs). For instance, recent metabolomic studies employing advanced spectro-chromatographic techniques have revealed a diverse chemical composition of comfrey plants, including polysaccharides, allantoin, benzoic and cinnamic acid derivatives, flavonoids, fatty acids, and unsaturated necine-structure-based PAs. The mechanisms underlying their anti-inflammatory, analgesic, wound-healing, anti-irritant, and osteo-regenerative properties were targeted in modern pharmacological setups. Thus, key compounds like allantoin, rosmarinic acid, globoidnans A and B, rabdosiin, and comfreyn A, have been identified as significant contributors to the anti-inflammatory and wound-healing effects of Symphytum-derived preparations. Despite their well-established clinical use, concerns about PAs-induced toxicity have prompted the development of novel PA remediation strategies, enabling the production of comfrey extracts with enhanced safety profiles that can meet the regulatory standards imposed by authorities.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Clarifying the nomenclature of Strychnosbredemeyeri and Lasiostoma (Loganiaceae).

Strychnos (Loganiaceae, Gentianales) is a large and pantropical genus of woody plants, ethnobotanically important as a source of many toxic alkaloids, including strychnine. Unfortunately, the status of numerous names at various ranks of Strychnos remains unresolved, including that of many specific or infraspecific taxa in the Neotropics. In this study, we address Strychnosbredemeyeri (basionym Lasiostomabredemeyeri), a species described in 1827 based on type material collected in Venezuela during the poorly documented Austrian Märter expedition (1783-1788). Strychnosbredemeyeri is an unarmed liana with solitary tendrils and axillary inflorescences that occurs in Neotropical rainforests and savannas in Brazil, Guyana, Trinidad and Tobago, and Venezuela. We clarify here the nomenclatural status of Lasiostoma Schreb., an illegitimate and superfluous genus currently in synonymy under Strychnos, and its former species Lasiostomabredemeyeri [= Strychnosbredemeyeri]. Also, we lectotypify S.pedunculata and S.trinitensis, both taxa currently synonyms of S.bredemeyeri.

An Atypical Case Report - Strychnos nux-vomica toxicity resulting from Vishtinduk Vati overdose linked with bradycardia

Strychnos nux-vomica, commonly known as poison nut, is a plant notorious for its toxic alkaloids, particularly strychnine and brucine. While cases of poisoning from nux-vomica ingestion have been documented, its occurrence following Vishtinduk Vati overdose is exceedingly rare. Here a case of a 55-year-old female with a known history of osteoarthritis who inadvertently overdosed on Vishtinduk Vati, an over-the-counter Ayurvedic medicine containing nux-vomica, in an attempt to alleviate her pain, led to severe poisoning characterized by classical symptoms of strychnine toxicity, including muscle twitching, vomiting and bradycardia, necessitating immediate medical intervention. This case highlights the dangers of self-medication with herbal remedies and the accessibility of potentially harmful over-the-counter Ayurvedic medications. It underscores the importance of healthcare providers opting for safer drug choices in daily practice and advocating against the indiscriminate use of herbal supplements, emphasizing the need for regulation and education to prevent such adverse outcomes.

A case of Gloriosa superba poisoning

ABSTRACT Gloriosa superba (GSb), or Glory Lily, is not an uncommon plant found in Sri Lanka. Every part of the plant is poisonous, especially the rhizome. It contains mainly colchicine and gloriocine which are toxic alkaloids. Fatalities following ingestion are rarely reported with current medical management. A 37-year-old male, with history of cannabis dependence and heroin abuse, ingested one and half of GSb rhizomes following a family dispute, witnessed by his family. He was hospitalized nearly eighteen hours later and he developed severe gastro-enteritis associated with nausea and vomiting. The patient’s presenting condition necessitated intensive care management for severe liver and renal failure. On the second day following admission he underwent haemodialysis and one cycle of plasma paresis but he ultimately succumbed due to unresponsive cardiac failure with arrhythmia. Subsequent autopsy examination revealed inflamed stomach and small intestinal mucosa with erosions, severe diffuse pulmonary haemorrhages with oedema, necrosis of liver and myocardium, and acute tubular necrosis. Multi-organ failure due to ingestion of GSb attributed to his death and manner of death was concluded as suicide following an inquest. This case report highlights the severity of effects of GSb poisoning including the effects on myocardium which is rarely encountered in clinical practice.

UPLC-TQD-MS/MS Method Validation for Quality Control of Alkaloid Content in Lepidium meyenii (Maca)-Containing Food and Dietary Supplements.

Lepidium meyenii Walp. (Brassicaceae), also known as Maca or Peruvian ginseng, is a common ingredient in food supplements with many claimed health benefits, such as improved endurance, increased energy level, and enhanced sexual properties. Due to potential toxicity of its chemicals, including alkaloids, some regulatory authorities, e.g., in Belgium, Germany, the United States, expressed concerns about the safe consumption of Maca root. However, due to the lack of commercial standards, no established analytical method currently exists for this purpose. The current project focuses on the quantitative determination of potentially toxic alkaloids from Maca. The current study presents the first analytical method for quality control of alkaloid content in Maca-containing food and dietary supplements, assessing the presence of 11 major compounds belonging to three different classes, i.e., imidazole, β-carboline, and pyrrole alkaloids. An accurate, rapid, and sensitive UPLC-TQD-MS/MS method is reported, which was fully validated according to the International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and SANTE/11312/2021 guidelines. To ensure the method's applicability and practicability in the absence of primary standards, validation of secondary standards (SSs) alongside primary standards (PSs) was also conducted for imidazole alkaloids. As a result, in Maca raw powder, total alkaloid content was found to vary from 418 to 554 ppm (mg/kg). Furthermore, all quantified imidazole alkaloids were ascertained to be the major alkaloids with the total content from 323 to 470 ppm in Maca raw powder, followed by the β-carboline and pyrrole alkaloids. It was also observed that the commercial preparation of finished products affects the total alkaloid content, evidenced by the large variation from 56 to 598 ppm. Ultimately, from a regulatory point of view, it seems advisible not to request the complete absence of the alkaloids but to impose a maximum level based on safety considerations. In addition to the analytical method, a low-cost, simple, and scalable synthetic scheme of macapyrrolins A, C, and G was reported for the first time.

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

The transcription factor StMYB113 regulates light-induced greening by modulating steroidal glycoalkaloid biosynthesis in potatoes (Solanum tuberosum L.)

During harvesting, storage, transportation, and processing, potato (Solanum tuberosum L.) tubers undergo greening after exposure to light, leading to the accumulation of toxic glycoside alkaloids, resulting in quality deterioration and economic losses. However, the underlying mechanisms are unclear. This study compared the transcriptome and proteome differences among four potato cultivars during the light-induced greening process, identifying 3,751 unique proteins (high confidence; ≥91.7%). The levels of enzymes involved in steroidal glycoalkaloid biosynthesis varied among the cultivars. In addition, coexpression network analysis of the transcriptomic data identified the transcription factor MYB113 (Soltu.DM.10G020780.1) as a potential positive regulator of steroidal glycoalkaloid biosynthesis. The dual-luciferase assay revealed that StMYB113 could bind to the promoters of steroidal glycoalkaloid biosynthesis-related genes and activate them. The transgenic lines overexpressing Solanum tuberosum L. Myb domain protein (StMYB113) exhibited greater mRNA abundance of these genes and elevated levels of steroidal glycoalkaloids. This study provided a theoretical basis for exploring the impact of light on the synthesis of solanine in potatoes.

The acute toxic effect of Chinese medicine Fuzi is exacerbated in kidney yang deficiency mice due to metabolic difference

Ethnopharmacological relevanceThe proper application of toxic medicines is one of the characteristics of traditional Chinese medicines, and the use of traditional Chinese medicines follows the principle of dialectical treatment. It is necessary to combine different “syndrome” or “disease” states with the toxicity of traditional Chinese medicines to form a reliable toxicity evaluation system. Fuzi, the lateral root of Aconitum carmichaelii Debx, is recognized as a panacea for kidney yang deficiency syndrome, however, its toxic effects significantly limit its clinical application. Aim of the studyHerein, our research aimed to explore the toxic effects of Fuzi on syndrome models, and tried to reveal the underlying mechanisms. Materials and methodsFirstly, the mouse model of kidney yang deficiency syndrome was established through intramuscular injection of 25 mg/kg hydrocortisone per day for 10 consecutive days. Then, the acute toxicity of Fuzi in normal mice and kidney yang deficiency model mice was explored. Finally, the plasma metabolite concentrations and liver CYP3A4 enzyme activity were analyzed to reveal the possible mechanisms of the different pharmacological and toxicological effects of Fuzi in individuals with different physical constitutions. ResultsIt was found that the treatment with Fuzi (138 g/kg) had serious toxic effects on kidney yang deficiency mice, leading to the death of 80% of the mice, whereas it showed no lethal toxicity in normal mice. This indicates that Fuzi induced greater toxicity in kidney yang deficiency mice than in normal ones. The liver CYP3A4 enzyme activity in kidney yang deficiency mice was decreased by 20% compared to the controls, resulting in slower metabolism of the toxic diester diterpenoid alkaloids in Fuzi. ConclusionIn conclusion, our study showed that changes of the metabolic enzyme activity in individuals with different syndromes led to different toxic effects of Chinese medicines, emphasizing the crucial importance of considering individual physical syndromes in the clinical application of traditional Chinese medicine, and the significance of conducting safety evaluations and dose predictions on animal models with specific syndromes for traditional Chinese medicines.

Understanding the toxicity mechanism of gelsemine in zebrafish

Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.

161 Effects of Sericea Lespedeza Supplementation on Steers Grazing Wild-Type Endophyte-Infected Tall Fescue

Abstract Fescue toxicosis poses a significant challenge to the United States beef industry, resulting in considerable economic losses. This syndrome arises from the consumption of tall fescue (Schedonorus arundinaceous) infected with the wild-type endophyte (WE; Epichloe coenophiala), which produces toxic alkaloids. The most effective solution for mitigating fescue toxicosis is renovating WE tall fescue pastures to novel endophyte-infected (NE) tall fescue. However, pasture renovation is costly and may not be feasible under certain conditions, with the economic profitability taking up to 3 yr. While the potential of condensed tannins (CTs) in specific leguminous forages to reduce the absorption of toxic alkaloids is recognized, their use as supplements remains underexplored. This study aims were to investigate the potential of CT-containing feed supplements, specifically sericea lespedeza (Lespedeza cuneata) pellets, in reducing the post-ingestive effects of fescue toxicosis in steers. Over two summers,12 steers were assigned to either Schedonorus arundinaceous (LES) or LES mixed with polyethylene glycol (LES + PEG) as a positive control for 12 wk. Body weight, hair retention score, rectal and extremities temperatures, cortisol concentrations, and lumen area of caudal arteries were collected at 4-wk intervals. Data were analyzed using a mixed-effect ANOVA test in SAS Studio 3.5. Steers on the LES diet exhibited significantly less (P &amp;lt; 0.05) hair retention scores compared with those on the LES + PEG diet. In 2021, steers on the LES diet showed greater (P = 0.0101) ADG, while in 2022, there was no difference (P = 0.9916) in ADG between the treatments. Steers on the LES diet displayed greater (P = 0.0332) tail skin temperatures and decreased (P &amp;lt; 0.0001) rectal temperatures compared with those on the LES + PEG diet. Hair cortisol concentrations were greater (P &amp;lt; 0.05) in steers on the LES + PEG diet than in those on the LES diet. Additionally, steers supplemented with the LES + PEG diet showed a 21.2% smaller caudal artery lumen area compared with those on the LES diet (P &amp;lt; 0.01). These findings underscore the potential of CTs in reducing the post-ingestive effects of fescue toxicosis. However, further research is needed to explore the complex mechanisms underlying these effects, establish the long-term efficacy of such interventions, and extend the investigation to include a broader range of physiological parameters affecting livestock health and performance.