Veratrum parviflorum poisoning: identification of steroidal alkaloids in patient blood and breast milk.

INTRODUCTION: The Veratrum genus is composed of plants containing a diverse set of steroidal alkaloids. Veratrum plant material has been utilized for centuries as herbal medicines, however the alkaloids have such a low therapeutic index that they are not used in modern medicine. Here we report an incident of inadvertent ingestion of V. parviflorum by hikers in Georgia that allowed detection, and in several instances identification of alkaloids from the plant, and correlated their presence within patient blood and breast milk specimens. CASE HISTORY: Eight patients, three male and five female, presented in the spring of 2020 and 2021 with symptoms requiring emergent medical attention after ingestion of Veratrum parviflorum. All patients believed the plants to be a local native species of wild leek, Allium tricoccum, locally known as ramps. Plants were identified using photographs as well as fresh and cooked plant material provided by patients, in consultation with botanists at the University of Georgia Herbarium. Written consent was obtained from all patients for collection of blood and breast milk specimens for laboratory identification of Veratrum alkaloids. METHODS: V. parviflorum plant material, and patient serum and breast milk were analyzed by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) to identify steroidal alkaloids. RESULTS: The V. parviflorum extract was confirmed to contain cyclopamine, veratramine, jervine, and muldamine. Two out of the eight patients had detectable concentrations of Veratrum alkaloids. Of the alkaloids identified in the plant, cyclopamine and jervine were detected within patient serum, and cyclopamine and veratramine were observed to be present in breast milk. DISCUSSION: Toxicity resulting from Veratrum steroidal alkaloids has primarily been reported from V. album and V. viride. This is the second report of V. parviflorum poisoning. The present work reports for the first time the presence of muldamine and jervine within V. parviflorum. This work provides the first instance of identification of Veratrum alkaloids in breast milk. Thus, the findings presented herein add to literature record causative agents contributing to the toxicity of V. parviflorum when ingested and potential for secondary poisoning through breastfeeding. CONCLUSION: V. parviflorum toxicity was observed to cause nausea, vomiting, hypotension, bradycardia, abdominal pain, light-headedness, blurred vision, and tingling in the arms. Patients experiencing mild symptoms improved with supportive care, IV fluids, and antiemetics, but hemodynamically unstable patients required atropine and vasopressors. This study demonstrated that more lipophilic Veratrum alkaloids can be passed along in breast milk, which suggests additional precautions may be critical to limit further poisonings.

Veratrum parviflorum: An Underexplored Source for Bioactive Steroidal Alkaloids.

Plants of the Veratrum genus have been used throughout history for their emetic properties, rheumatism, and for the treatment of high blood pressure. However, inadvertent consumption of these plants, which resemble wild ramps, induces life-threatening side effects attributable to an abundance of steroidal alkaloids. Several of the steroidal alkaloids from Veratrum spp. have been investigated for their ability to antagonize the Hedgehog (Hh) signaling pathway, a key pathway for embryonic development and cell proliferation. Uncontrolled activation of this pathway is linked to the development of various cancers; most notably, basal cell carcinoma and acute myeloid leukemia. Additional investigation of Veratrum spp. may lead to the identification of novel alkaloids with the potential to serve as chemotherapeutics. V. parviflorum is a relatively uncommon species of Veratrum that resides in the southeastern regions of North America. The phytochemical profile of this plant remains largely unexplored; however, bioactive steroidal alkaloids, including cyclopamine, veratramine, veratridine, and verazine were identified in its extract. The structural elucidation and bioactivity assessment of steroidal alkaloids in lesser abundance within the extract of V. parviflorum may yield potent Hh pathway inhibitors. This review seeks to consolidate the botanical and phytochemical information regarding V. parviflorum.

Review: Veratrum californicum Alkaloids.

Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17-45 Veratrum spp., Veratrum californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. californicum root and rhizome via liquid chromatography-mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.

Instrumentation for Routine Analysis of Acrylamide in French Fries: Assessing Limitations for Adoption.

The purpose of this experimental review was to detect acrylamide in French fries using methods most adaptable to the food process industry for quality control assessment of products. French fries were prepared at different cook times using the same fryer oil over a five-day period to assess the influence of oil degradation and monitor trends in acrylamide formation. Acrylamide detection was performed using LC-MS, GC-MS and FT-NIR. The low levels of acrylamide produced during frying, low molecular weight of the analyte, and complexity of the potato matrix make routine acrylamide measurement challenging in a well-outfitted analytical lab with trained personnel. The findings of this study are presented from the perspective of pros and cons of each acrylamide measurement method in enough detail for food processors to appraise the method that may work best for them based on their available instrumentation and extent of personnel training.

Determination of Organosulfides from Onion Oil.

Qualitative and semi-quantitative analysis of organosulfides extracted from oil obtained by steam distillation of yellow onions was performed by gas chromatography-mass spectrometry (GC-MS). The extraction efficiency of organosulfides from onion oil was evaluated across four solvents: dichloromethane; diethyl ether; n-pentane; and hexanes. Analysis of solvent extracted organosulfides by GC-MS provided qualitative results that support the use of dichloromethane over other solvents based on identification of 27 organosulfides from the dichloromethane extract as compared to 10 from diethyl ether; 19 from n-pentane; and 17 from hexanes. Semi-quantitative evaluation of organosulfides present in the dichloromethane extract was performed using diallyl disulfide as the internal reference standard. Three organosulfides were detected in the extract at ≥5 mg/kg; 18 organosulfides between 3-5 mg/kg; and six organosulfides at <3 mg/kg. The E/Z isomers of 1-propenyl propyl trisulfide were among the most prevalent components extracted from the onion oil across all solvents; and 3,6-diethyl-1,2,4,5-tetrathiane was among the most abundant organosulfides in all solvents except hexanes. The method described here for the extraction of organosulfides from steam distilled onion oil surveys common solvents to arrive at a qualitative and semi-quantitative method of analysis for agricultural products involving onions; onion oil; and secondary metabolites of Allium spp.