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Journal of Agricultural and Food... Jul 2014In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial... (Review)
Review
In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was found to inhibit the hedgehog (Hh) signaling pathway, which plays a critical role in embryonic development. More recently, aberrant Hh signaling has been implicated in several types of cancer. Thus, inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. A brief history of cyclopamine and cyclopamine derivatives investigated for the treatment of cancer is presented.
Topics: Animal Feed; Animals; Hedgehog Proteins; Holoprosencephaly; Humans; Mutation; Neoplasms; Plant Extracts; Sheep, Domestic; Signal Transduction; Teratogens; Veratrum; Veratrum Alkaloids
PubMed: 24754790
DOI: 10.1021/jf5005622 -
Toxins Jul 2022Jervine, protoveratrine A (proA), and protoveratrine B (proB) are alkaloids that are presented in some remedies obtained from , such as . This paper reports on a...
Jervine, protoveratrine A (proA), and protoveratrine B (proB) are alkaloids that are presented in some remedies obtained from , such as . This paper reports on a single-center pilot cardiotoxic mechanism study of jervine, proA, and proB in case series. The molecular aspects were studied via molecular dynamic simulation, molecular docking with cardiac sodium channel Na1.5, and machine learning-based structure-activity relationship modeling. HPLC-MS/MS method in combination with clinical events were used to analyze alkaloid cardiotoxicity in patients. Jervine demonstrates the highest docking score (-10.8 kcal/mol), logP value (4.188), and p value (9.64) compared with proA and proB. Also, this compound is characterized by the lowest calculated IC. In general, all three analyzed alkaloids show the affinity to Na1.5 that highly likely results in cardiotoxic action. The clinical data of seven cases of intoxication by confirms the results of molecular modeling. Patients exhibited nausea, muscle weakness, bradycardia, and arterial hypotension. The association between alkaloid concentrations in blood and urine and severity of patient condition is described. These experiments, while primary, confirmed that jervine, proA, and proB contribute to cardiotoxicity by Na1.5 inhibition.
Topics: Alkaloids; Cardiotoxicity; Humans; Molecular Docking Simulation; Pilot Projects; Tandem Mass Spectrometry; Veratrum; Veratrum Alkaloids
PubMed: 35878228
DOI: 10.3390/toxins14070490 -
Current Protein & Peptide Science 2018Isosteroidal alkaloids are a category of promising bioactive compounds which mostly exist in plants of genus Veratrum and Fritillaria. The pharmacological activities of... (Review)
Review
Isosteroidal alkaloids are a category of promising bioactive compounds which mostly exist in plants of genus Veratrum and Fritillaria. The pharmacological activities of isosteroidal alkaloids include antihypertensive, antitussive, anti-inflammatory, antithrombosis, among others. Recently, some studies show that this kind of alkaloids exhibited significant antitumor activity. To the best of our knowledge, there is no review focusing on their antitumor activity and mechanism of their antitumor activity. To fill the gap, in this review, we summarized antitumor effects of the isosteroidal alkaloids from genus Veratrum and Fritillaria on different tumors and the mechanisms of their antitumor activity. In conclusion, this kind of alkaloids has extensive antitumor activity, and there are several main mechanisms of their antitumor activity, including the Hedgehog signaling pathway, caspase-3 dependent apoptosis, cell cycle, and autophagy.
Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Cell Cycle; Fritillaria; Hedgehog Proteins; Humans; Neoplasms; Signal Transduction; Veratrum; Veratrum Alkaloids
PubMed: 28059041
DOI: 10.2174/1389203718666170106103747 -
Frontiers in Plant Science 2022Pimacao is a traditional Chinese folk medicine and is the main component of the famous Chinese herbal remedy "Yunnan Baiyao" for its significant analgesic activity in...
Pimacao is a traditional Chinese folk medicine and is the main component of the famous Chinese herbal remedy "Yunnan Baiyao" for its significant analgesic activity in the treatment of wounds. Due to increases in consumption, its wild population is now difficult to find, and adulterant from the same genus has occurred. However, this is challenging to distinguish the species of in Pimacao using dried roots and rhizomes or medicinal powder. ITS2 sequences and steroidal alkaloids by the non-targeted and pseudo-targeted metabolomics methods were taken advantage of establishing an effective identification method. Based on the ITS2 sequence, metabolite profiling of steroidal alkaloids and morphological characteristics, the classification of two distinct subspecies in has been reinforced. In addition, the new subspecies subsp. was collected in China for the first time. The ITS2 sequence could be used in the identification of , , , and , but is insufficient for intraspecific identification. Simultaneously, 147 variables were labeled by non-targeted analysis accomplished utilizing an ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UPLC-ESI-QE-Orbitrap-MS) system consisting of an Orbitrap QE HF-X. Followed by a pseudo-targeted analysis method developed for the Qtrap 6500-plus mass spectrometry system coupled with an ESI source, 29 labeled steroidal alkaloids detected by the MRM mode could distinguish between four species. Notably, 25 labeled steroidal alkaloids could distinguish between three closely related species. These have the potential to be used as markers for identification. Furthermore, there were several variables with statistical differences between two subspecies of and populations of , , and .
PubMed: 35481147
DOI: 10.3389/fpls.2022.831562 -
Chemistry & Biodiversity Feb 2020Veratrum plant contains a family of compounds called steroidal alkaloids which have been previously reported to cause DNA damage and blood pressure decrease in vivo....
Veratrum plant contains a family of compounds called steroidal alkaloids which have been previously reported to cause DNA damage and blood pressure decrease in vivo. In this study, the antihypertensive effects and DNA damage in brain cells of 12 steroidal alkaloids separated from Veratrum plant were all evaluated to develop a relationship among chemical structure, antihypertensive activity and neurotoxicity by utilization of chemical principal component analysis (PCA) and hierarchical cluster analysis (HCA). Twelve steroidal alkaloids markedly reduced high blood pressure of hypertensive mice and also similarly induced varying degrees of DNA single-strand breaks in mouse cerebellum and cerebral cortex after oral administration. On the basis of the PCA and HCA results, it was suggested that the 3-carboxylic esters and benzene group play a core role in the DNA damage of brain cells, while more hydroxy groups in the A-ring and B-ring structure of jervine-type alkaloid led to stronger antihypertensive activity. The primary structure, activity and neurotoxicity relationship were discussed briefly.
Topics: Administration, Oral; Animals; Antihypertensive Agents; Blood Pressure; Cerebral Cortex; Cluster Analysis; DNA Damage; Mice; Plant Extracts; Principal Component Analysis; Structure-Activity Relationship; Veratrum; Veratrum Alkaloids
PubMed: 31961474
DOI: 10.1002/cbdv.201900473 -
Phytochemistry Reviews : Proceedings of... Sep 2014Plants belonging to the genus have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical...
Plants belonging to the genus have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical investigations revealed a host of steroidal alkaloids in species, some of which are potent bioactives. This review discusses species that grow in North America with a focus on the medicinal history of these plants and the steroidal alkaloids they contain. While significant reviews have been devoted to singularly describing the plant species within the genus (botany), the staggering breadth of alkaloids isolated from these and related plants (phytochemistry), and the intricacies of how the various alkaloids act on their biological targets (physiology and biochemistry), this review will straddle the margins of the aforementioned disciplines in an attempt to provide a unified, coherent picture of the plants of North America and the medicinal uses of their bioactive steroidal alkaloids.
PubMed: 25379034
DOI: 10.1007/s11101-013-9328-y -
Fitoterapia Apr 2023Three new steroidal alkaloids, veratrasines A - C (1-3), along with ten known analogues (4-13) were isolated from the roots of Veratrum stenophyllum. Their structures...
Three new steroidal alkaloids, veratrasines A - C (1-3), along with ten known analogues (4-13) were isolated from the roots of Veratrum stenophyllum. Their structures were elucidated by NMR and HRESIMS data and comparison with the reported data in the literatures. A plausible biosynthetic pathway for 1 and 2 were proposed. Compounds 1, 3, and 8 showed moderate cytotoxic activity against MHCC97H and H1299 cell lines.
Topics: Veratrum; Molecular Structure; Alkaloids; Plant Roots; Steroids; Veratrum Alkaloids
PubMed: 36848963
DOI: 10.1016/j.fitote.2023.105464 -
Journal of Medicinal Chemistry Sep 2019Important steps in embryonic development are governed by the Hedgehog (Hh) signaling pathway, an evolutionary conserved signal transduction cascade. However, Hh activity... (Review)
Review
Important steps in embryonic development are governed by the Hedgehog (Hh) signaling pathway, an evolutionary conserved signal transduction cascade. However, Hh activity not only is crucial during embryo formation but also is involved in adult tissue repair and in several malignancies. Particularly due to its link to cancer, small molecule Hh pathway inhibitors have been developed and the first compounds have been approved for use in Hh-driven basal cell carcinoma. Almost all advanced Hh inhibitors target the critical signaling component Smoothened (SMO), but preclinical research has identified additional compounds that can block the Hh pathway along its entire signaling cascade, which, in light of emerging drug resistance occurring with SMO inhibitors, is of high importance. Herein we give an overview on currently known Hh pathway inhibitors, delineating their respective strengths and weaknesses and describing potential drug targeting strategies to interfere with Hh signaling in different cancer settings.
Topics: Animals; Antineoplastic Agents; Carcinoma, Basal Cell; Drug Approval; Drug Design; Hedgehog Proteins; Humans; Ligands; Molecular Targeted Therapy; Neoplasms; Receptors, G-Protein-Coupled; Signal Transduction; Smoothened Receptor; Veratrum Alkaloids
PubMed: 30986059
DOI: 10.1021/acs.jmedchem.9b00188 -
Sudebno-meditsinskaia Ekspertiza 2020The problem of laboratory diagnosis of acute and fatal poisoning by hellebore, which is possible when used in traditional medicine, the erroneous use of hellebore...
The problem of laboratory diagnosis of acute and fatal poisoning by hellebore, which is possible when used in traditional medicine, the erroneous use of hellebore preparations orally or use of various types of this plant for food, remains relevant. Currently, in the practice of chemical-toxicological laboratories and the bureau of forensic medical examination there is no single approach to the laboratory diagnosis of such poisoning. The diagnosis is most often based on anamnesis. In this regard, the development and validation of a legally significant methodology for the determination of hellebore alkaloids in various biological objects seems relevant. The physicochemical and toxic properties of alkaloids of various types of hellebore are characterized. It was shown that for the identification of hellebore alkaloids, it is advisable to use HPLC-MS/MS as the most sensitive and specific instrumental method corresponding to the characteristics of hellebore alkaloids (high molecular weight, high thermal lability, high polarity).
Topics: Helleborus; Poisoning; Tandem Mass Spectrometry; Veratrum; Veratrum Alkaloids
PubMed: 32686389
DOI: 10.17116/sudmed20206304134 -
Journal of Ethnopharmacology Sep 2024Veratrum nigrum L. (V. nigrum) is a well-known herb with a lengthy history of use in Asian and European countries. V. nigrum has been traditionally used to treat... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Veratrum nigrum L. (V. nigrum) is a well-known herb with a lengthy history of use in Asian and European countries. V. nigrum has been traditionally used to treat epilepsy, hypertension, malignant sores, and stroke, and it possesses emetic and insecticide properties.
AIM OF THE REVIEW
This review summarized the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, and toxicity of V. nigrum as well as its incompatibility with other herbs. Current challenges in the use of V. nigrum and possible future research directions were also discussed.
MATERIALS AND METHODS
Information on V. nigrum was collected from electronic databases such as PubMed, Google Scholar, Web of Science, CNKI, and WanFang DATA; Masterpieces of Traditional Chinese Medicine; local Chinese Materia Medica Standards; and relevant documents.
RESULTS
In ethnomedical practice, V. nigrum has been used as an emetic and insecticide. Approximately 137 compounds have been isolated from V. nigrum, including alkaloids, stilbenes, flavonoids, organic acids, and esters. Its crude extracts and compounds have shown various effects, including anticancer, hypotensive, insecticidal, and antimicrobial activities as well as the ability to improve hemorheological abnormalities. Pharmacokinetic studies have indicated that veratramine (VAM) and jervine have high bioavailability and possibly enterohepatic circulation. In addition, the sex-related pharmacokinetic differences in V. nigrum alkaloids warrant further attention. Toxicological studies have indicated that cevanine-type alkaloids and VAM may be the main toxic components of V. nigrum, and purine metabolism disorders may be related to V. nigrum toxicity. Furthermore, the neurotoxicity and embryotoxicity of V. nigrum have also been observed. The quality control of V. nigrum and the mechanism underlying its incompatibility with other herbs also deserve further research and refinement.
CONCLUSION
This review summarized the existing information on V. nigrum, laying the foundation for further studies on this herb and its safe use. Among the various compounds present in V. nigrum, steroid alkaloids are the most numerous and have high content; furthermore, they are closely related to the pharmacological effects of V. nigrum, but their toxicity can not also be ignored. Given that toxicity is a critical issue limiting the clinical application of V. nigrum, more toxicological studies on V. nigrum and its active ingredients, especially steroid alkaloids, should be conducted in the future to further explore its toxicity targets and the underlying mechanisms and to provide more evidence and recommendations to enhance the safety of its clinical application.
Topics: Humans; Ethnopharmacology; Animals; Phytochemicals; Veratrum; Plant Extracts; Phytotherapy
PubMed: 38663784
DOI: 10.1016/j.jep.2024.118219