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Phytomedicine : International Journal... Nov 2023Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it...
BACKGROUND
Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions.
PURPOSE
This study aimed to investigate the short-term and long-term hypotensive profiles of different components of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action.
RESULTS
Total Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension.
CONCLUSION
This work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO-ET homeostasis.
Topics: Humans; Animals; Rats; Antihypertensive Agents; Niacin; Veratrum Alkaloids; Hypertension; Data Analysis; Niacinamide
PubMed: 37647672
DOI: 10.1016/j.phymed.2023.155033 -
Chemical Communications (Cambridge,... Jan 2023Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from , and its structure was established...
Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from , and its structure was established spectroscopic analyses and X-ray diffraction. A plausible biosynthetic pathway for 1 is proposed. Bioassy exhibits moderate anti-inflammatory activities and .
Topics: Alkaloids; Plant Extracts; Veratrum; Steroids; Anti-Inflammatory Agents; Antineoplastic Agents; Molecular Structure
PubMed: 36511292
DOI: 10.1039/d2cc06073f -
Journal of Analytical Toxicology Feb 2022Veratrum poisonings are described in the toxicology literature as multiple Veratrum species grow in different parts of the Northern Hemisphere and are occasionally...
Veratrum poisonings are described in the toxicology literature as multiple Veratrum species grow in different parts of the Northern Hemisphere and are occasionally ingested by mistake. Veratrum toxicity is attributed to the steroidal alkaloids contained in all parts of the plant. In Russia, Veratrum poisonings are more common since there is an over-the-counter Veratrum lobelianum-based tincture, Veratrum Aqua (VA), which is topically used for the treatment of lice infestation. Despite its toxicity, VA is misused in traditional medicine as a remedy for alcohol use disorder. We describe four cases of VA poisoning that occurred in Moscow, Russia. Three main V. lobelianum alkaloids (jervine, protoveratrine A (proA) and protoveratrine B) were determined in patient plasma and urine samples using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Here, we describe a novel validated LC-MS-MS method for jervine and proA quantification. A simple and rapid liquid-liquid extraction with methyl tert-butyl ether was utilized for analyte extraction. Chromatographic separation was achieved using a Poroshell 120 EC-C18 column, and the total run time was 14 min. The lower limit of quantification was 0.1 ng/mL for jervine and proA in both plasma and urine. Biological samples were obtained upon hospital admission and during treatment, thus enabling to get a better understanding of the alkaloid elimination profile. Upon admission, plasma concentrations of jervine (concentration range: 0.10-5.01 ng/mL) prevailed over proA (concentration range: 0-0.67 ng/mL). At this time, proA already reached maximum concentrations in urine (concentration range: 0.15-37.70 ng/mL). Maximum concentrations of jervine in urine were observed 24 h after admission (concentration range: 0.10-9.55 ng/mL). In all cases, plasma concentrations of Veratrum alkaloids correlated with condition severity. Since none of the patients confirmed VA intake, instrumental analysis was the basis for the definitive diagnosis of VA poisoning.
Topics: Alkaloids; Chromatography, Liquid; Humans; Mass Spectrometry; Veratrum; Veratrum Alkaloids
PubMed: 33559680
DOI: 10.1093/jat/bkab019 -
Journal of the American Chemical Society Oct 2023A concise and enantioselective total synthesis of the alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS)...
A concise and enantioselective total synthesis of the alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a synthesis of the -6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji-Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite diastereocontrol, and a late-stage ring-closing metathesis (RCM) reaction to forge the central tetrasubstituted olefin.
Topics: Cyclization; Alkenes; Veratrum Alkaloids; Stereoisomerism
PubMed: 37782691
DOI: 10.1021/jacs.3c09085 -
Phytochemical Analysis : PCA Jun 2024Veratrum alkaloids have gained attention due to their toxic effects and potential pharmaceutical applications, particularly in cancer and cardiology. Over 200 alkaloids...
INTRODUCTION
Veratrum alkaloids have gained attention due to their toxic effects and potential pharmaceutical applications, particularly in cancer and cardiology. Over 200 alkaloids are found in species of the Veratrum genus. The alkaloid composition and concentrations can greatly vary in plants depending on factors like species, plant part, location, season, weather, or nutrients.
OBJECTIVE
This study aims an analytical approach to analyze and quantify Veratrum alkaloids in different plant parts of Veratrum species. The purpose is to contribute essential alkaloid concentration data for future research on the pharmacological and toxicological aspects of Veratrum alkaloids.
METHODS
This study focuses on five Veratrum alkaloids (cevadine, jervine, protoveratrine A, veratramine, and veratridine) in three Veratrum species (Veratrum album L., Veratrum californicum Durand, and Veratrum nigrum L.) collected from four German botanical gardens (Dresden, Leipzig, Marburg, and Schellerhau). A liquid-liquid extraction method and a sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method operating in multiple reaction monitoring (MRM) mode were applied for the alkaloid determination.
RESULTS
Quantification revealed varying alkaloid concentrations among plant parts and Veratrum species in the μg/g to mg/g range. Protoveratrine A exhibited the highest content, while veratramine concentrations were generally lower. Especially in fruit, roots and rootstock of Veratrum album L. alkaloid concentrations were significant high.
CONCLUSION
The developed HPLC-MS/MS method successfully determined Veratrum alkaloid concentrations in plant samples. The study contributes valuable data on Veratrum alkaloid distribution in different species and plant parts, crucial for understanding their potential medicinal and toxicological significance.
PubMed: 38863228
DOI: 10.1002/pca.3401 -
Scientific Reports May 2023Veratrum (Melanthiaceae; Liliales) is a genus of perennial herbs known for the production of unique bioactive steroidal alkaloids. However, the biosynthesis of these...
Veratrum (Melanthiaceae; Liliales) is a genus of perennial herbs known for the production of unique bioactive steroidal alkaloids. However, the biosynthesis of these compounds is incompletely understood because many of the downstream enzymatic steps have yet to be resolved. RNA-Seq is a powerful method that can be used to identify candidate genes involved in metabolic pathways by comparing the transcriptomes of metabolically active tissues to controls lacking the pathway of interest. The root and leaf transcriptomes of wild Veratrum maackii and Veratrum nigrum plants were sequenced and 437,820 clean reads were assembled into 203,912 unigenes, 47.67% of which were annotated. We identified 235 differentially expressed unigenes potentially involved in the synthesis of steroidal alkaloids. Twenty unigenes, including new candidate cytochrome P450 monooxygenases and transcription factors, were selected for validation by quantitative real-time PCR. Most candidate genes were expressed at higher levels in roots than leaves but showed a consistent profile across both species. Among the 20 unigenes putatively involved in the synthesis of steroidal alkaloids, 14 were already known. We identified three new CYP450 candidates (CYP76A2, CYP76B6 and CYP76AH1) and three new transcription factor candidates (ERF1A, bHLH13 and bHLH66). We propose that ERF1A, CYP90G1-1 and CYP76AH1 are specifically involved in the key steps of steroidal alkaloid biosynthesis in V. maackii roots. Our data represent the first cross-species analysis of steroidal alkaloid biosynthesis in the genus Veratrum and indicate that the metabolic properties of V. maackii and V. nigrum are broadly conserved despite their distinct alkaloid profiles.
Topics: Veratrum; Transcriptome; Alkaloids; Gene Expression Profiling; Veratrum Alkaloids; Steroids; Cytochrome P-450 Enzyme System
PubMed: 37211560
DOI: 10.1038/s41598-023-35429-5 -
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 -
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 -
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