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[Advances in studies on steroidal alkaloids and their pharmacological activities in genus Veratrum].Zhongguo Zhong Yao Za Zhi = Zhongguo... Nov 2020Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1~A-69), veratramine...
Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1~A-69), veratramine type(B-1~B-21), jervanine type(C-1~C-31), solanidine type(D-1~D-10) and verazine type(E-1~E-53), respectively, have been isolated and identified in the genus Veratrum. Their pharmacological activities mainly focused on decreasing blood pressure, anti-platelet aggregation and anti-thrombosis, anti-inflammatory and analgesic, and antitumor effect. This paper classified and summarized the 184 kind of steroidal alkaloids from the Veratrum plants and their major pharmalogical activities in order to provide the scientific basis for the further development and utilization of active alkaloids.
Topics: Alkaloids; Analgesics; Platelet Aggregation; Steroids; Veratrum
PubMed: 33350228
DOI: 10.19540/j.cnki.cjcmm.20200612.201 -
Pharmaceuticals (Basel, Switzerland) Jan 2024contains steroidal alkaloids that function as inhibitors of hedgehog (Hh) signaling, a pathway involved in the growth and differentiation of cells and normal tissue...
contains steroidal alkaloids that function as inhibitors of hedgehog (Hh) signaling, a pathway involved in the growth and differentiation of cells and normal tissue development. This same Hh pathway is abnormally active for cell proliferation in more than 20 types of cancer. In this current study, alkaloids have been extracted from the root and rhizome of , followed by their separation into five fractions using high performance liquid chromatography. Mass spectrometry was used to identify the presence of twenty-five alkaloids, nine more than are commonly cited in literature reports, and the Bruker Compass Data Analysis software was used to predict the molecular formula for every detected alkaloid. The Gli activity of the raw extract and each fraction were compared to 0.1 µM cyclopamine, and fractions 1, 2, and 4 showed increased bioactivity through suppression of the Hh signaling pathway. Fractions 2 and 4 had enhanced bioactivity, but fraction 1 was most effective in inhibiting Hh signaling. The composition of fraction 1 consisted of veratrosine, cycloposine, and potential isomers of each.
PubMed: 38256956
DOI: 10.3390/ph17010123 -
Frontiers in Genetics 2023is the main ingredient for Chinese folk medicine known as "Pimacao" due to its unique alkaloids. A diverse class of plant-specific metabolites having key...
is the main ingredient for Chinese folk medicine known as "Pimacao" due to its unique alkaloids. A diverse class of plant-specific metabolites having key pharmacological activities. There are limited studies on alkaloid synthesis and its metabolic pathways in plants. To elucidate the alkaloid pathway and identify novel biosynthetic enzymes and compounds in , transcriptome and metabolome profiling has been conducted in leaves and roots. The transcriptome of leaves and roots yielded 190,161 unigenes, of which 33,942 genes expressed differentially (DEGs) in both tissues. Three enriched regulatory pathways (isoquinoline alkaloid biosynthesis, indole alkaloid biosynthesis and tropane, piperidine and pyridine alkaloid biosynthesis) and a considerable number of genes such as , , , , , , were discovered in association with the biosynthesis of alkaloids in leaves and roots. Some transcription factor families, i.e., , , , , , , , , , , and were also found to have a prominent role in regulating the synthesis of alkaloids and steroidal alkaloids in the leaves and roots of . The metabolome analysis revealed 74 significantly accumulated metabolites, with 55 differentially accumulated in leaves compared to root tissues. Out of 74 metabolites, 18 alkaloids were highly accumulated in the roots. A novel alkaloid compound viz; 3-Vanilloylygadenine was discovered in root samples. Conjoint analysis of transcriptome and metabolome studies has also highlighted potential genes involved in regulation and transport of alkaloid compounds. Here, we have presented a comprehensive metabolic and transcriptome profiling of tissues. In earlier reports, only the roots were reported as a rich source of alkaloid biosynthesis, but the current findings revealed both leaves and roots as significant manufacturing factories for alkaloid biosynthesis.
PubMed: 36741317
DOI: 10.3389/fgene.2023.1023433 -
Microbiology Spectrum Feb 2022The limited number of available effective agents necessitates the development of new antifungals. We report that jervine, a jerveratrum-type steroidal alkaloid isolated...
The limited number of available effective agents necessitates the development of new antifungals. We report that jervine, a jerveratrum-type steroidal alkaloid isolated from Veratrum californicum, has antifungal activity. Phenotypic comparisons of cell wall mutants, K1 killer toxin susceptibility testing, and quantification of cell wall components revealed that β-1,6-glucan biosynthesis was significantly inhibited by jervine. Temperature-sensitive mutants defective in essential genes involved in β-1,6-glucan biosynthesis, including , , , , and , were hypersensitive to jervine. In contrast, point mutations in or its paralog produced jervine resistance, suggesting that jervine targets Kre6 and Skn1. Jervine exhibited broad-spectrum antifungal activity and was effective against human-pathogenic fungi, including Candida parapsilosis and Candida krusei. It was also effective against phytopathogenic fungi, including Botrytis cinerea and Puccinia recondita. Jervine exerted a synergistic effect with fluconazole. Therefore, jervine, a jerveratrum-type steroidal alkaloid used in pharmaceutical products, represents a new class of antifungals active against mycoses and plant-pathogenic fungi. Non-Candida albicans species (NCAC) are on the rise as a cause of mycosis. Many antifungal drugs are less effective against NCAC, limiting the available therapeutic agents. Here, we report that jervine, a jerveratrum-type steroidal alkaloid, is effective against NCAC and phytopathogenic fungi. Jervine acts on Kre6 and Skn1, which are involved in β-1,6-glucan biosynthesis. The skeleton of jerveratrum-type steroidal alkaloids has been well studied, and more recently, their anticancer properties have been investigated. Therefore, jerveratrum-type alkaloids could potentially be applied as treatments for fungal infections and cancer.
Topics: Alkaloids; Antifungal Agents; Candida; Cell Wall; Fungi; Humans; Mycoses; Plant Extracts; Veratrum; beta-Glucans
PubMed: 35019680
DOI: 10.1128/spectrum.00873-21 -
Journal of Ethnopharmacology Nov 2019Veratrum taliense is traditionally used TCMs in Yunnan province of China for pain and inflammation. Previous research and clinical applications have shown that V....
ETHNOPHARMACOLOGICAL RELEVANCE
Veratrum taliense is traditionally used TCMs in Yunnan province of China for pain and inflammation. Previous research and clinical applications have shown that V. taliense had significant analgesic activity. Jevine-type alkaloids were shown to be one of the anti-inflammatory and analgesic agents from V. taliense. However, other types of compounds from V. taliense related to its traditional use remains unknown.
AIM OF THE STUDY
To identify veratramine-type steroidal alkaloids with analgesic effects from the roots and rhizomes of V. taliense.
MATERIALS AND METHODS
Compounds were isolated from the roots and rhizomes of V. taliense by chromatographic separation. Their structures were elucidated based on UV, IR, NMR and MS spectra data. Analgesic activity was assessed with acetic acid-induced writhing in mice model.
RESULTS
Seven new veratramine-type alkaloids were isolated from the roots and rhizomes of V. taliense. They all exhibited significant analgesic activity, of which alkaloids 1 and 4 were more potent antalgic than the well-known analgesic drug, pethidine.
CONCLUSIONS
The veratramine-type alkaloids from V. taliense may serve as new leads for the discovery of analgesic drugs.
Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Female; Male; Mice, Inbred ICR; Pain; Phytochemicals; Plant Roots; Veratrum
PubMed: 31381955
DOI: 10.1016/j.jep.2019.112137 -
Fitoterapia Nov 2020Two new steroidal alkaloids (1-2), together with seven known related steroidal alkaloids (3-9), were isolated from the rhizomes of Veratrum nigrum L. Their structures...
Two new steroidal alkaloids (1-2), together with seven known related steroidal alkaloids (3-9), were isolated from the rhizomes of Veratrum nigrum L. Their structures were elucidated by extensive spectroscopic analysis, and by comparison with literature data. Compound 1 possessed a rare 1, 3-oxazolidine unit within varazine-type alkaloids, and 2 was a 9-hydroxy-4-one derivative of 3-veratroylgermine. All isolates were evaluated inhibit tomato yellow leaf curl virus (TYLCV) activity. Compounds 5 and 7 (40 μg/mL) showed a significant anti-TYLCV activity in the host Nicotiana benthamiana with inhibition rates 74.6% and 63.4%, respectively, which are higher than that of the positive control ningnanmycin (51.4%).
Topics: Alkaloids; Begomovirus; China; Molecular Structure; Phytochemicals; Plant Diseases; Rhizome; Steroids; Nicotiana; Veratrum
PubMed: 32979466
DOI: 10.1016/j.fitote.2020.104731 -
Nature Nov 2017
Topics: Belgium; Biological Products; Biomimetic Materials; Cantharidin; Cevanes; Chemistry Techniques, Synthetic; Chemistry, Organic; France; Gonadal Steroid Hormones; History, 20th Century; History, 21st Century; Humans; Quinine; Steroids; United States
PubMed: 29189811
DOI: 10.1038/d41586-017-07527-8 -
Archives of Biochemistry and Biophysics Apr 2024Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological... (Review)
Review
Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological setting, it is associated with oncogenesis and is responsible for disease progression and poor clinical outcomes. Hedgehog signaling mediates downstream actions via Glioma Associated Oncogene Homolog (GLI) transcription factors. Inhibiting Hh signaling is an important oncological strategy in which inhibitors of the ligands SMO or GLI have been looked at. This review briefly narrates the Hh ligands, signal transduction, the target genes involved and comprehensively describes the numerous inhibitors that have been evaluated for use in various neoplastic settings.
Topics: Humans; Hedgehog Proteins; Signal Transduction; Veratrum Alkaloids; Neoplasms
PubMed: 38432565
DOI: 10.1016/j.abb.2024.109952 -
Nature Chemical Biology Apr 2015The Hedgehog pathway is critical for animal development and has been implicated in multiple human malignancies. Despite great interest in targeting the pathway... (Review)
Review
The Hedgehog pathway is critical for animal development and has been implicated in multiple human malignancies. Despite great interest in targeting the pathway pharmacologically, many of the principles underlying the signal transduction cascade remain poorly understood. Hedgehog ligands are recognized by a unique receptor system that features the transporter-like protein Patched and the G protein-coupled receptor (GPCR)-like Smoothened (SMO). The biochemical interaction between these transmembrane proteins is the subject of intensive efforts. Recent structural and functional studies have provided great insight into the small-molecule regulation of SMO through identification of two distinct ligand-binding sites. In this Perspective, we review these recent findings and relate them to potential mechanisms for the endogenous regulation of SMO.
Topics: Allosteric Site; Amino Acid Sequence; Animals; Cell Membrane; Drosophila; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Ligands; Mice; Molecular Conformation; Molecular Sequence Data; Mutation; Neoplasms; Patched Receptors; Protein Binding; Protein Structure, Tertiary; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Sequence Homology, Amino Acid; Smoothened Receptor; Sterols; Veratrum Alkaloids
PubMed: 25785427
DOI: 10.1038/nchembio.1776 -
Tissue & Cell Apr 2024Peiminine (PMI) is an active alkaloid sourced from Fritillaria thunbergii, which has been shown to suppress the development of a variety of tumors. Whereas, the roles...
BACKGROUND
Peiminine (PMI) is an active alkaloid sourced from Fritillaria thunbergii, which has been shown to suppress the development of a variety of tumors. Whereas, the roles and precise mechanism of PMI in breast cancer (BC) development remain not been clarified.
METHODS
The cytotoxic effect of PMI on MCF-10A and BC cell lines (MCF-7 and BT-549) were assessed by MTT and LDH release assay. Cell proliferation was evaluated by EdU staining. Levels of Malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH) activity and iron assay were measured by Enzyme linked immunosorbent assay (ELISA) kits, respectively. Transmission Electron Microscope was performed to observe mitochondrial morphological structure. Immunofluorescence, immunohistochemistry, and western blot were conducted to examine protein levels, respectively. Xenograft model was used to confirm cellular findings.
RESULTS
PMI treatment reduced the viability and enhanced LDH level of MCF-7 and BT-549 cells in a time- and concentration-dependent manner, and further suppressed cell proliferation in vitro and tumor growth in vivo. Subsequently, PMI administration resulted in significant increases of ROS, MDA and iron levels, reduction of GSH activity as well as mitochondrial shrinkage and GPX4 reduction, while all these phenomena could be rescued by ferrostatin-1. Mechanistically, PMI treatment led to promoted Nrf2 expression and its nuclear translocation, as well as it's downstream protein HO-1 and NQO1 expressions. Notably, ML-385, a Nrf2 specific inhibitor, greatly reversed the anti-tumor effects and pro-ferroptosis role of PMI in BC cells.
CONCLUSION
Taking these finding together, PMI could stimulate ferroptosis to inhibit BC tumor growth by activating Nrf2-HO-1 signaling pathway.
Topics: Humans; Female; Breast Neoplasms; NF-E2-Related Factor 2; Ferroptosis; Reactive Oxygen Species; Signal Transduction; Iron; Cevanes
PubMed: 38412577
DOI: 10.1016/j.tice.2024.102323