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The Alkaloids. Chemistry and Biology 2015This survey on steroidal alkaloids of the Veratrum and Solanum family isolated between 1974 and 2014 includes 187 compounds and 197 references. New developments in the... (Review)
Review
This survey on steroidal alkaloids of the Veratrum and Solanum family isolated between 1974 and 2014 includes 187 compounds and 197 references. New developments in the chemistry and biology of this family of natural products with a special focus on the medicinal relevance of the jervanine alkaloid cyclopamine are discussed.
Topics: Animals; Antineoplastic Agents, Phytogenic; Diosgenin; Humans; Molecular Structure; Solanaceous Alkaloids; Veratrum Alkaloids
PubMed: 25845062
DOI: 10.1016/bs.alkal.2014.11.002 -
Molecules (Basel, Switzerland) Sep 2021spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of plants have been used for the treatment of ailments... (Review)
Review
spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of 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 spp., 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 alkaloids are cyclopamine (), veratramine (), isorubijervine (), muldamine (), cycloposine (), and veratrosine (). Recent inspection of the ethanolic extract from root and rhizome via liquid chromatography-mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine () etioline (), tetrahydrojervine () dihydrojervine (), 22-keto-26-aminocholesterol (). For each alkaloid identified or proposed in , this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.
Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Biological Products; Humans; Neoplasms; Veratrum
PubMed: 34641477
DOI: 10.3390/molecules26195934 -
Ecotoxicology and Environmental Safety Jul 2022Fine particulate matter (PM2.5) exposure can cause lung injury and a large number of respiratory diseases. Sipeimine is a steroidal alkaloid isolated from Fritillaria...
Fine particulate matter (PM2.5) exposure can cause lung injury and a large number of respiratory diseases. Sipeimine is a steroidal alkaloid isolated from Fritillaria roylei which has been associated with anti-inflammatory, antitussive and antiasthmatic properties. In this study, we explored the potential effects of sipeimine against PM2.5-induced lung injury in Sprague Dawley rats. Sipeimine alleviated lung injury caused by PM2.5 and decreased pulmonary edema, inflammation and the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the bronchoalveolar lavage fluid. In addition, sipeimine upregulated the glutathione (GSH) expression and downregulated the expression of 4-hydroxynonenal (4-HNE), tissue iron and malondialdehyde (MDA). The downregulation of proteins involved in ferroptosis, including nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1) and solute carrier family 7 member 11 (SLC7A11) was reversed by sipeimine. The administration of RSL3, a potent ferroptosis-triggering agent, blocked the effects of sipeimine. Using network pharmacology, we found that the effects of sipeimine were presumably mediated through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. A PI3K inhibitor (LY294002) blocked the PI3K/Akt signaling pathway and reversed the effects of sipeimine. Overall, this study suggested that the protective effect of sipeimine against PM2.5-induced lung injury was mainly mediated through the PI3K/Akt pathway, ultimately leading to a reduction in ferroptosis.
Topics: Animals; Cevanes; Ferroptosis; Lung Injury; NF-E2-Related Factor 2; Network Pharmacology; Particulate Matter; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley
PubMed: 35567927
DOI: 10.1016/j.ecoenv.2022.113615 -
Journal of the American Chemical Society Sep 2023The alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of...
The alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of (-)-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels-Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the synthesis of this highly oxidized alkaloid.
Topics: Stereoisomerism; Cyclization; Biological Products; Carbon; Cycloaddition Reaction
PubMed: 37683183
DOI: 10.1021/jacs.3c08039 -
Journal of Ethnopharmacology Jul 2022"Li-Lu", the roots and rhizomes of Veratrum grandiflorum (Melianthiaceae), has been historically used as a traditional folk medicine for the treatment of wrist pain,...
ETHNOPHARMACOLOGICAL RELEVANCE
"Li-Lu", the roots and rhizomes of Veratrum grandiflorum (Melianthiaceae), has been historically used as a traditional folk medicine for the treatment of wrist pain, fractures, sores, and inflammation in Yunnan Province, China. However, the anti-inflammatory and analgesic studies of this plant have seldom reported.
AIM OF THE STUDY
To evaluate the anti-inflammatory and analgesic properties related to the traditional usage of V. grandiflorum both in vitro and in vivo, and further explore the accurate bioactive compounds from the medicinal plant.
MATERIALS AND METHODS
Phytochemical investigation was carried out by chromatographic methods and their structures were established based on extensive spectra and comparison with corresponding data in the reported literatures. Anti-inflammatory activities were assessed by the suppression of lipopolysaccharide-activated inflammatory mediators in RAW 264.7 macrophage cells in vitro. Furthermore, anti-inflammatory and analgesic effects were evaluated based on carrageenan-induced paw edema and acetic acid-stimulated writhing in mice.
RESULTS
The methanol extract (ME) of V. grandiflorum significantly alleviated the paw edema caused by carrageenan and the writhing numbers induced by acetic acid. Subsequent phytochemical investigation led to isolated of 21 steroidal alkaloids, including seven new compounds, veragranines C-I (1-7). Anti-inflammatory test indicated that steroidal alkaloids could decrease the expression of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells at a concentration of 5.0 μg/ml in vitro, comparable to DXM. Moreover, five new steroidal alkaloids (2, 4, 5, 6, and 7) and two major steroidal alkaloids (9 and 13) significantly decreased the numbers of writhing in mice at the doses of 0.5 and/or 1.0 mg/kg (p < 0.01/0.05), roughly comparable to Dolantin™ at 10.0 mg/kg.
CONCLUSIONS
The investigation supported the traditional use of V. grandiflorum and provided new steroidal alkaloids as potent analgesic agents.
Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; China; Edema; Lipopolysaccharides; Mice; Mice, Inbred ICR; Phytochemicals; Plant Extracts; Veratrum
PubMed: 35452774
DOI: 10.1016/j.jep.2022.115290 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2022The genus is composed of plants containing a diverse set of steroidal alkaloids. plant material has been utilized for centuries as herbal medicines, however the...
INTRODUCTION
The genus is composed of plants containing a diverse set of steroidal alkaloids. 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 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 All patients believed the plants to be a local native species of wild leek, , 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 alkaloids.
METHODS
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 extract was confirmed to contain cyclopamine, veratramine, jervine, and muldamine. Two out of the eight patients had detectable concentrations of 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 steroidal alkaloids has primarily been reported from and . This is the second report of poisoning. The present work reports for the first time the presence of muldamine and jervine within . This work provides the first instance of identification of alkaloids in breast milk. Thus, the findings presented herein add to literature record causative agents contributing to the toxicity of when ingested and potential for secondary poisoning through breastfeeding.
CONCLUSION
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 alkaloids can be passed along in breast milk, which suggests additional precautions may be critical to limit further poisonings.
Topics: Female; Humans; Veratrum; Milk, Human; Veratrum Alkaloids; Alkaloids; Plant Poisoning
PubMed: 36301078
DOI: 10.1080/15563650.2022.2132166 -
Medicinal Research Reviews Jan 2016Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades... (Review)
Review
Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases.
Topics: Alkaloids; Androgens; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Cell Line, Tumor; Diosgenin; Estrogens; Humans; Mice; Neoplasms; Solanaceous Alkaloids; Steroids; Tomatine; Veratrum Alkaloids
PubMed: 25820039
DOI: 10.1002/med.21346 -
Molecules (Basel, Switzerland) Aug 2022Plants of the genus have been used throughout history for their emetic properties, rheumatism, and for the treatment of high blood pressure. However, inadvertent... (Review)
Review
Plants of the 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 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 spp. may lead to the identification of novel alkaloids with the potential to serve as chemotherapeutics. is a relatively uncommon species of 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 may yield potent Hh pathway inhibitors. This review seeks to consolidate the botanical and phytochemical information regarding
Topics: Alkaloids; Hedgehog Proteins; Phytochemicals; Plant Extracts; Steroids; Veratrum
PubMed: 36014585
DOI: 10.3390/molecules27165349 -
Nature Jul 2021Biomolecular condensates have emerged as an important subcellular organizing principle. Replication of many viruses, including human respiratory syncytial virus (RSV),...
Biomolecular condensates have emerged as an important subcellular organizing principle. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers.
Topics: Animals; Antiviral Agents; Biomolecular Condensates; Cell Line; Female; Humans; Inclusion Bodies; Lung; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus, Human; Transcription Factors; Veratrum Alkaloids; Viral Proteins; Virus Replication
PubMed: 34234347
DOI: 10.1038/s41586-021-03703-z