Active Metabolites in the Chronic Hepatotoxicity of Pyrrolizidine Alkaloids,including Otonecine Esters

WHEN she reported the chronic hepatotoxicity of the alkaloids senkirkine and hydroxysenkirkine, which are esters of the aminoalcohol otonecine, Schoental¹ suggested that 1,2-epoxides rather than pyrrolic derivatives^2,3 are the active metabolites of hepatotoxic pyrrolizidine alkaloids. We have results which confirm the hepatotoxicity of otonecine esters but argue against the suggested involvement of 1,2-epoxides.     

植物中吡咯里西啶生物碱的检测与分析

吡咯里西啶生物碱广泛分布于植物界。很多吡咯里西啶生物碱对动物和人类有严重的毒性作用,包括肝脏毒性,肺脏毒性,致癌作用,致突变作用和神经毒性等。本文综述了植物中吡咯里西啶生物碱的分离,纯化,检测与分析。     

Two New Alkaloids from Fuzi and Their Metabolites Study

Former study suggests alkaloids from herbs of Aconitum genus plants possess excellent bioactivities, which exert great value for related deeper chemical constituent investigation. Herein, chemical isolation was performed and four alkaloids were isolated from Fuzi, of which two were new ones, and the other two were reported NMR data for the first time. Their chemical structures were identified by NMR data, high resolution MS, UV and IR analysis. Additionally, the MS fragmentation patterns were explored, formerly, that of hetisane alkaloid was rarely reported, and fragmentation mechanism of the diagnostic ion was proposed. Based on these fragment pathway, metabolites and metabolic pathways of four compounds were investigated in rat liver microsomes using UPLC−Q/TOF−MS, and dehydrogenation product was firstly found from metabolites of hetisane alkaloid.     

Ideamine N-Oxides: Pyrrolizidine Alkaloids Sequestered by the Danaine Butterfly,Idea leuconoe

Two new pyrrolizidine alkaloids, ideamines A and B, together with other analogs (lycopsamine and parsonsine) were isolated in the N-oxide forms from adult bodies of the Apocynaceae-feeding danaine butterfly, Idea leuconoe. Ideamine A was characterized as a homolog of lycopsamine, in which the viridifloric acid moiety was replaced by a 2-ethyl-2,3-dihydroxybutanoic moiety. Likewise, ideamine B was identified as a nor-derivative of parsonsine, in which the trachelanthic acid moiety was replaced by a 2-ethyl-2,3-dihydroxybutanoic moiety diastereomeric to the necic acid from ideamine A.     

Pyrrolizidine alkaloids from Alkanna tinctoria

Three pyrrolizidine alkaloids were isolated from Alkanna tinctoria and their structures analysed by spectroscopic methods. One of them is new and the name dihydroxytriangularine is proposed for it.     

Non-toxic pyrrolizidine alkaloids from Eupatorium semialatum

The leaves of Eupatorium semialatum were investigated for the occurrence of pyrrolizidine alkaloids. Although this type of alkaloids generally occurs in the Eupatorieae, only unusual non-toxic pyrrolizidines of the tussilagin type were identified. All compounds are methyl esters of the corresponding beta-amino acids.     

Detection and Toxicity Evaluation of Pyrrolizidine Alkaloids in Medicinal Plants Gynura bicolor and Gynura divaricata Collected from Different Chinese Locations

Two edible plants in Southeast Asia, Gynura bicolor and G . divaricata , are not only known to be nutritive but also useful as medicinal herbs. Previous phytochemical investigation of Gynura species showed the presence of hepatotoxic pyrrolizidine alkaloids (PA s), indicating the toxic risk of using these two plants. The present study was designed to analyze the distribution of PA components and tried to evaluate the preliminary toxicity of these two Gynura species. Eight samples of G . bicolor and G . divaricata from five different Chinese locations were collected and their specific PA s were qualitatively characterized by applying an UPLC /MS /MS spectrometry method. Using a pre‐column derivatization HPLC method, the total retronecine ester‐type PA s in their alkaloids extracts were quantitatively estimated as well. Finally, their genotoxicity was investigated with an effective high‐throughput screening method referred to as Vitotox ? test and their potential cytotoxicity was tested on HepG2 cells. It was found that different types of PA s were widely present in Gynura species collected from south of China. Among them, no significant genotoxic effects were detected with serial concentrations through the present in vitro assay. However, the cytotoxicity assay of Gynura plants collected from Jiangsu displayed weak activity at the concentration of 100 mg/ml. It is important to note that this research validates in part the indication that the use of Gynura species requires caution.     

Pyrrolizidine alkaloids from Lithospermum canescens Lehm

Seven pyrrolizidine alkaloids (PAs) have been isolated from Lithospermum canescens and their structures determined by spectroscopical methods. Besides the known lycopsamine, O7-acetyl-lycopsamine and O7-acetylintermedine four new PAs were found. Their structures are O7-(3-hydroxy-3-methyl-butanoyl)-O9-(+)-trachelanthoyl-heliotridine (= O7-(3-hydroxy-3-methyl-butanoyl)-rinderine = canescine), O7-(3-hydroxy-3-methyl-butanoyl)-O9-(-)-viridifloryl-heliotridine (= O7-(3-hydroxy-3-methyl-butanoyl)-echinatine = canescenine and their O13-acetyl-derivatives (= acetylcanescine; acetylcanescenine).     

Pyrrolizidine alkaloids from Ageratum houstonianum Mill.

Four pyrrolizidine alkaloids (PA) were isolated from Ageratum houstonianum and their structures elucidated by spectroscopical methods. Besides the already known lycopsamine three new PA were found. Their structures are the 2S-2-hydroxy-2,3-dimethyl-butanoyl-O(9) as well as the O(7) esters of retronecine and the O(9) derivative of heliotridine.     

Pyrrolizidine alkaloids from Neurolaena lobata

Neurolaena lobata was investigated for the occurrence of pyrrolizidine alkaloids. The untypical methyl ester alkaloids tussilagine, isotussilagine and their possible biosynthetic precursor 2-pyrrolidineacetic acid were found in the methanolic leaf extract. As previously found for Arnica species and Tussilago farfara, all methyl esters are artifacts derived from the corresponding acids during Soxhlet extraction. The occurrence of toxic necines, often found in the Senecioneae, could be ruled out.     

Pyrrolizidine alkaloids from Senecio cacaliaster

Four pyrrolizidine alkaloids have been isolated from Senecio cacaliaster and their structures analysed by spectroscopic methods (IR, mass, ¹H, ¹³CNMR). One of them is new and the name sencalenine (3) is proposed. Alkaloids O⁷-senecioylretronecine (1) and 7-senecioyl-9-sarracinylretronecine (2) have recently been identified elsewhere. The fourth is bulgarsenine (4) which was isolated from a Senecio species before.     

Pyrrolizidine alkaloids from seeds of Crotalaria scassellatii

Three pyrrolizidine alkaloids were isolated from the seeds of Crotalaria scassellatii. Axillaridine and axillarine were the two major alkaloids whereas the third minor alkaloid was a new compound. Its structure was determined as desoxyaxillarine.     

Molecular Characterization of Sheep Ruminal Enrichments that Detoxify Pyrrolizidine Alkaloids by Denaturing Gradient Gel Electrophoresis and Cloning

An enrichment of strictly anaerobic bacteria from ovine rumen fluid, which has previously been named L4M2, is known to detoxify animal hepatotoxins from the pyrrolizidine alkaloid family. These toxins are present in the tansy ragwort plant (Senecio jacobaea). These plants have been described in livestock animals’ range forages in regions of the world such as the Northwest United States and South Africa. The bacterial enrichment was characterized by molecular cloning techniques and by the molecular fingerprinting technique of denaturing gradient gel electrophoresis (DGGE). Phylogenetic analysis of the enrichment revealed that the consortium is composed of no more than five putative bacterial species which associated to the Anaerovibrio, Desulfovibrio, Megasphaera, Prevotella, and Synergistes generas. These are all known to exist in the upper gastrointestinal tract of ruminant animals. This work improved upon previous attempts to characterize the consortium by obtaining nearly full-length ribosomal 16S rDNA sequences through cloning. The DGGE results were directly compared to the cloning data by polymerase chain reaction (PCR) amplifying eight phylogenetically representative clones and analyzing them by DGGE. Direct DGGE analysis of the enrichment displayed greater 16S diversity than the clone library used in this study, suggesting that at least one of the organisms present in the enrichment comprises less than 1% of the total cell population. These data will be used to further refine the enrichment in hopes of future use as a probiotic, which could be administered to animals challenged by the presence of tansy ragwort in their forage.     

Influence of Endophyte and Water Regime Upon Tall Fescue Accessions. II. Pyrrolizidine and Ergopeptine Alkaloids

Alkaloids, along with specific environmental conditions, havebeen associated with both detrimental and beneficial aspectsof endophyte (Acremonium coenophialum Morgan-Jones et Gams)infected tall fescue (Festuca arundinacea Schreb.) associations.Benefits to the plant accrue through reduced herbivory, whereasdetriment to the animal occurs as altered grazing behaviourand reduced productivity. A controlled environment study wasconducted to examine pyrrolizidine and ergopeptine alkaloidconcentration of four tall fescue accessions as influenced byendophyte status and water regime. Endophyte-free plants weredevoid of ergopeptine alkaloid and contained little, if any,pyrrolizidine alkaloid. Leaf blade tissue of endophyte-infectedisolines contained a range of both ergopeptine (256 to 1633ng g^–1) and pyrrolizidine (92 to 450 µg g^–1)alkaloid concentrations. Water deficit generally increased alkaloidconcentration. Alkaloid yield, based upon concentration andtissue d. wt, showed that significant increase in ergopeptineand pyrrolizidine alkaloid in leaf tissue was associated withwater deficit and was due to actual increased synthesis andnot simply decreased phytomass. Leaf and pseudostem (leaf sheathand stem base) tissue alkaloid concentrations indicated differentaccumulation patterns for ergopeptine and pyrrolizidine alkaloids.Ergopeptine alkaloid yield increased in water-stressed pseudostem,whereas pyrrolizidine alkaloid yield decreased in some, butnot all accessions. The range of host genotype/endophyte biotyperesponse offers the possibility to select associations whichproduce few deleterious effects in animals yet maintain highforage productivity and persistence. Festuca arundinacea, Acremonium coenophialum, tall fescue genotypes, water stress, N-formyl and N-acetyl loline, ergovaline     

Occurrence of Indole Alkaloids among Secondary Metabolites of Soil Aspergillus Spp.

The occurrence of indole alkaloids among secondary fungal metabolites was studied in species of the genus Aspergillus, isolated from soils that were sampled in various regions of Russia (a total of 102 isolates of the species A. niger, A. phoenicis, A. fumigatus, A. flavus, A. versicolor, A. ustus, A. clavatus, and A. ochraceus). Clavine alkaloids were represented by fumigaclavine B, which was formed by A. fumigatus. -Cyclopiazonic acid was formed by isolates of A. fumigatus, A. flavus, A. versicolor, A. phoenicis, and A. clavatus. The occurrence of indole-containing diketopiperazine alkaloids was documented for isolates of A. flavus, A. fumigatus, A. clavatus, and A. ochraceus. No indole-containing metabolites were found among the metabolites of A. ustus or A. niger.