Search

One new otonecine-type pyrrolizidine alkaloid secopetasitenine (1), along with petasitenine (fukinotoxine, 2), neopetasitenine (3), and senkirkine (4), was isolated from the whole plant of Petasites japonicus. The structure of 1 was determined by spectroscopic analyses and chemical conversion from the known alkaloid petasitenine (2).

The honey bee pollen/nectar diet is rich in bioactive phytochemicals and recent studies have demonstrated the potential of phytochemicals to influence honey bee disease resistance. To unravel the role of dietary phytochemicals in honey bee health it is essential to understand phytochemical uptake, bioavailability, and metabolism but presently limited knowledge exists. With this study we aim to build a knowledge foundation. For 5 days, we continuously fed honey bees on eight individual phytochemicals and measured the concentrations in whole and dissected bees by HPLC-MS/MS. Ample phytochemical metabolization was observed, and only 6–30% of the consumed quantities were recovered. Clear differences in metabolization rates were evident, with atropine, aucubin, and triptolide displaying significantly slower metabolism. Phytochemical gut uptake was also demonstrated, and oral bioavailability was 4–31%, with the highest percentages observed for amygdalin, triptolide, and aucubin. We conclude that differences in the chemical properties and structure impact phytochemical uptake and metabolism.

The honey bee pollen/nectar diet is rich in bioactive phytochemicals and recent studies have demonstrated the potential of phytochemicals to influence honey bee disease resistance. To unravel the role of dietary phytochemicals in honey bee health it is essential to understand phytochemical uptake, bioavailability, and metabolism but presently limited knowledge exists. With this study we aim to build a knowledge foundation. For 5 days, we continuously fed honey bees on eight individual phytochemicals and measured the concentrations in whole and dissected bees by HPLC-MS/MS. Ample phytochemical metabolization was observed, and only 6-30% of the consumed quantities were recovered. Clear differences in metabolization rates were evident, with atropine, aucubin, and triptolide displaying significantly slower metabolism. Phytochemical gut uptake was also demonstrated, and oral bioavailability was 4-31%, with the highest percentages observed for amygdalin, triptolide, and aucubin. We conclude that differences in the chemical properties and structure impact phytochemical uptake and metabolism.

Emilia sonchifolia (L.) DC. (Lilac tasselflower, Zi Bei Cao ) is used in Asian countries for food or medicinal purposes. We have investigated the hepatotoxic pyrrolizidine alkaloids (PAs) contained in E. sonchifolia . The objective was to determine profile and quantity of the PAs in E. sonchifolia samples that were collected from several towns in Taiwan. Pyrrolizidine alkaloids were isolated and purified from the aqueous acid extracts by use of strong cation exchange-solid phase extraction (SCX-SPE). Alkaloid extracts were analyzed using gas–chromatography mass spectrometry (GC–MS). Eleven PAs of two types were identified in E. sonchifolia (by type): (1) retronecine bases, senecionine, seneciphylline and integerrimine; (2) otonecine bases, senkirkine, otosenine, neosenkirkine, petasitenine, acetylsenkirkine, desacetyldoronine, acetylpetasitenine, and doronine. Quantification of the individual PAs was determined by six-point linear regression curves in the range of 25–400 μg/mL of senkirkine and senecionine. The PAs were found in all plant organs of E. sonchifolia . Senkirkine was the major PA identified with concentrations up to 53.8 μg/g of dry herb. The average total PA concentration varied from a low of 33.3 μg/g to a high of 93.9 μg/g dry herb. This study will provide important information to public consumers regarding the health risk of PA-containing E. sonchifolia .

For several years the use of the medicinal plant Tussilago farfara (coltsfoot) has been restricted in Austria and Germany due to the content of toxic pyrrolizidine alkaloids. In order to meet the demand for crude drug an in vitro collection of clones was established as a basis for the selection of suitable lines. Analyses of the alkaloid content showed that some clones were free of the toxic compounds. One of these clones has now been cultivated in the field for several years, and permanent monitoring confirms that the quality is in accordance with the requirements of the legislation. By large scale culture of the variety Tussilago farfara `Wien it is now possible to provide material for pharmaceutical and dietary purposes and thus to re-introduce this medicinal plant to the market.

A colour reaction for unsaturated pyrrolizidine alkaloids is made applicable for the first time to otonecine alkaloids and is used for the photometric determination of senkirkine in coltsfoot. The method allows the determination of 1 μg of alkaloid in 1 g of dried drug (i.e. 1 p.p.m.) and is therefore a useful alternative to the more exacting gas chromatographic determination. © 1997 by John Wiley & Sons, Ltd.

The supposed non-pyrrolizidine compound prepared from senkirkine and chloroplatinic acid, and thought to be a reaction product or an impurity in the senkirkine, is shown to be senkirkine chloroplatinate by a reprocessing of the crystallographic data.

A Phytochemical Investigation Of The Overground Parts Of Sencio Glabellus Resulted In Isolation and Identification Of Five Pyrrolizidine Alkaloids: Florosenine (Acetylotosenine), Senecionine, Integerrimine, Otosenine and Senkirkine, By Comparison With Authentic Samples. Separation Of The First Three Of These Alkaloids From Otosenine and Senkirkine Was Realized By A Simple Liquid/Liquid Extraction Procedure Which Is Reported. This Is The First Report Of The Occurrence Of Florosenine, Otosenine and Senkirkine In S. Glabellus.

A simple and rapid micellar electrokinetic chromatography (MEKC) method was developed for the separation and determination of four toxic pyrrolizidine alkaloids (PAs) (senkirkine, senecionine, retrorsine, and seneciphylline) in two traditional Chinese herbal medicines (Qian liguang and Kuan donghua). Separation was performed in the running buffer consisting of 20 mM borate, 30 mM SDS, and 20% methanol at pH 9.1. With the optimized separation conditions, four PAs were separated in 17 min by a single run. The calibration curves showed good linearity with correlation efficiencies (R(2)) between 0.9940 and 0.9988. RSDs in migration time and peak area were 0.31, 0.40, 0.39, 0.48% and 3.28, 3.48, 4.16, 3.42% for senkirkine, senecionine, retrorsine, and seneciphylline, respectively. Limits of detection (S/N = 3) varied from 1.19 to 2.70 microg/mL. The proposed method was applied to determine the PAs extracted from Chinese herbal medicines (Qian liguang and Kuan donghua). PA of senkirkine in Kuan donghua was detected and the amount was found to be 79.1 microg/g. The results obtained indicate that the proposed MEKC method could potentially become an effective alternative tool for qualification control and quantitative analysis of herbal medicines in pharmaceutical industry.

Tussilagine, isotussilagine, neo-tussilagine and neo-isotussilagine were isolated from Ligularia sibirica whereas Tephroseris integrifolia was found to contain senkirkine, otosenine, hydroxysenkirkine and 07-angeloylheliotridine. The structures were determined using spectroscopical methods (GC-MS, NMR).

Petasites jragrans (Vill.) C. Presl., auch Vanille-Pestwurz genannt, ist heimisch in Tripolitanien [...]

In this study the clinical signs and pathology of five plant poisonings and a mycotoxicosis affecting the nervous system of domestic ruminants in southern Africa are described. For comparative purposes, an inherited storage disease (bèta-mannosidosis) and a drug-induced neurotoxicosis (closantel overdose) are also presented. The aims of this thesis were: (1) to document the pathology of those conditions where detailed descriptions were lacking, (2) to study the light and transmission electron microscopical lesions from a differential diagnostic perspective, and, (3) to consider the possible causative mechanisms of the nervous lesions. A novel lysosomal storage disease in goats induced by the plant Ipomoea carnea is reported. Analysis of plant material confirmed the presence of swainsonine and two glycosidase inhibitors, namely, calystegine B2 and calystegine C1. The storage disease is analogous to the lysosomal storage disease in ruminants induced by ingestion of locoweeds (Astragalus and Oxytropis spp.) and poison peas (Swainsona spp) and closely mimics inherited a-mannosidosis in animals. ?-Mannosidosis is documented in Hereford calves, a breed not previously known to be afflicted by this inherited disorder. The condition was biochemically confirmed by an absence of lymphocyte ?-mannosidase activity in one of the affected calves. ‘Maldronksiekte’ in cattle, caused by ingestion of the plant Solanum kwebense, is characterised by degeneration, necrosis and loss of cerebellar Purkinje cells and, to a lesser extent, neurons in cerebellar nuclei. Affected Purkinje neurons were either swollen, pale and finely vacuolated or shrunken and more eosinophilic than normal. In the present study, some Purkinje cells and neurons in cerebellar nuclei stained strongly with Canavalia ensiformis (ConA) agglutinin and weakly with Triticum vulgaris (WGA) and succinyl-WGA (S-WGA) agglutinins. The neuronal lesions were not caused by apoptosis as tested by a commercial deoxyuridine triphosphate nick-end labeling (TUNEL) method. Based on the selective involvement and nature of lesions in cerebellar Purkinje cells, ‘maldronksiekte’ is classified as an acquired cerebellar cortical degeneration and not a lysosomal storage disease. Four toxic myelinopathies are described; three are induced by plants (Helichrysum argyrosphaerum, Ornithogalum prasinum and O. saundersiae and Crotalaria sparthioides) and one is caused by overdosage of the anthelmintic compound closantel. The four conditions are characterized by indistinguishable spongy changes (status spongiosis) in the central nervous system caused by splitting of myelin lamellae at the intraperiod line consistent with myelin oedema. The brain lesions in toxicity with Crotalaria sparthioides in cattle are typical for hepatic encephalopathy secondary to cirrhosis. The pyrrolizidine alkaloid senkirkine was isolated from toxic plant material. Primary toxic retinal degeneration was present in poisoning by Helichrysum argyrosphaerum and in closantel poisoning. Finally, the pathology of acute and chronic Aspergillus clavatus intoxication in cattle is studied. In acute cases there is chromatolysis and cytoplasmic vacuolation particularly of motor neurons in the ventral horns throughout the spinal cord. Electron microscopy revealed disintegration of Nissl bodies, abundant free ribosomes and increased numbers of mitochondria and dense bodies comparable to the axonal reaction. In chronic cases fed sorghum beer residues, extensive, bilaterally symmetrical Wallerian degeneration in ascending and descending tracts throughout the length of the spinal cord were seen. This neuromycotoxicosis is classified as a neuronopathy/axonopathy. A histological feature of all the conditions that are described in this thesis is the presence of vacuolation of varying severity in neurons and/or neuropil in the central nervous system of affected animals. Apart from the storage diseases, the pathogenesis of the nervous lesions is largely unknown.

In this study the clinical signs and pathology of five plant poisonings and a mycotoxicosis affecting the nervous system of domestic ruminants in southern Africa are described. For comparative purposes, an inherited storage disease (bèta-mannosidosis) and a drug-induced neurotoxicosis (closantel overdose) are also presented. The aims of this thesis were: (1) to document the pathology of those conditions where detailed descriptions were lacking, (2) to study the light and transmission electron microscopical lesions from a differential diagnostic perspective, and, (3) to consider the possible causative mechanisms of the nervous lesions. A novel lysosomal storage disease in goats induced by the plant Ipomoea carnea is reported. Analysis of plant material confirmed the presence of swainsonine and two glycosidase inhibitors, namely, calystegine B2 and calystegine C1. The storage disease is analogous to the lysosomal storage disease in ruminants induced by ingestion of locoweeds (Astragalus and Oxytropis spp.) and poison peas (Swainsona spp) and closely mimics inherited a-mannosidosis in animals. ?-Mannosidosis is documented in Hereford calves, a breed not previously known to be afflicted by this inherited disorder. The condition was biochemically confirmed by an absence of lymphocyte ?-mannosidase activity in one of the affected calves. ‘Maldronksiekte’ in cattle, caused by ingestion of the plant Solanum kwebense, is characterised by degeneration, necrosis and loss of cerebellar Purkinje cells and, to a lesser extent, neurons in cerebellar nuclei. Affected Purkinje neurons were either swollen, pale and finely vacuolated or shrunken and more eosinophilic than normal. In the present study, some Purkinje cells and neurons in cerebellar nuclei stained strongly with Canavalia ensiformis (ConA) agglutinin and weakly with Triticum vulgaris (WGA) and succinyl-WGA (S-WGA) agglutinins. The neuronal lesions were not caused by apoptosis as tested by a commercial deoxyuridine triphosphate nick-end labeling (TUNEL) method. Based on the selective involvement and nature of lesions in cerebellar Purkinje cells, ‘maldronksiekte’ is classified as an acquired cerebellar cortical degeneration and not a lysosomal storage disease. Four toxic myelinopathies are described; three are induced by plants (Helichrysum argyrosphaerum, Ornithogalum prasinum and O. saundersiae and Crotalaria sparthioides) and one is caused by overdosage of the anthelmintic compound closantel. The four conditions are characterized by indistinguishable spongy changes (status spongiosis) in the central nervous system caused by splitting of myelin lamellae at the intraperiod line consistent with myelin oedema. The brain lesions in toxicity with Crotalaria sparthioides in cattle are typical for hepatic encephalopathy secondary to cirrhosis. The pyrrolizidine alkaloid senkirkine was isolated from toxic plant material. Primary toxic retinal degeneration was present in poisoning by Helichrysum argyrosphaerum and in closantel poisoning. Finally, the pathology of acute and chronic Aspergillus clavatus intoxication in cattle is studied. In acute cases there is chromatolysis and cytoplasmic vacuolation particularly of motor neurons in the ventral horns throughout the spinal cord. Electron microscopy revealed disintegration of Nissl bodies, abundant free ribosomes and increased numbers of mitochondria and dense bodies comparable to the axonal reaction. In chronic cases fed sorghum beer residues, extensive, bilaterally symmetrical Wallerian degeneration in ascending and descending tracts throughout the length of the spinal cord were seen. This neuromycotoxicosis is classified as a neuronopathy/axonopathy. A histological feature of all the conditions that are described in this thesis is the presence of vacuolation of varying severity in neurons and/or neuropil in the central nervous system of affected animals. Apart from the storage diseases, the pathogenesis of the nervous lesions is largely unknown.

Three new monoterpene glucosides, solidagin A, B, and C (1–3), together with two known alkaloids, senecionine (4) and senkirkine (5), were isolated from Senecio solidagineus, and their structures were elucidated on the basis of 1D and 2D NMR spectral analysis.

Two toxic pyrrolizidine alkaloids were isolated from Senecio leucanthemifolius and six from Senecio rodriguezii. Their structures were determined by spectroscopic methods.

The supposed non-pyrrolizidine compound prepared from senkirkine and chloroplatinic acid, and thought to be a reaction product or an impurity in the senkirkine, is shown to be senkirkine chloroplatinate by a reprocessing of the crystallographic data.

Stereochemistry at C-18 of petasitenine, the carcinogenic alkaloid isolated from Petasites japonicus Maxim. was established by chemical and spectral means: the structure of petasitenine was thus determined completely, which is represented by (1). Transformation of petasitenine (1) into senkirkine (3) was achieved by low valent tungusten complexes.

A gas-chromatographical method is described on which seven pyrrolizidine alkaloids (Fuchsisenecionine, Senecionine, Senecivernine, Senkirkine, Retrorsine, O (7)-Angelylheliotridine and Heliotrine) are determinated in a qualitative way and their ratio of concentration in Senecio fuchsii, vernalis, inaequidens and ovirensis, ssp. gaudinii.

The mutagenicities of 7 pyrrolizidine alkaloids to Salmonella typhimurium TA100 were demonstrated by a modified Ames's method. The pyrrolizidine alkaloids found to be mutagenic were clivorine, fukinotoxin, heliotrine, lasiocarpine, ligularidine, LX201 and senkirkine. Pre-incubation of these alkaloids with S9 mix and bacteria in a liquid medium was essential for demonstration of their mutagenicities.

Genotoxicity of heliotrine, monocrotaline, seneciphylline and senkirkine was studied with the sister-chromatid exchange assay in V79 Chinese hamster cells. Exposure to these pyrrolizidine alkaloids, in the presence of co-cultured primary chick embryo hepatocytes, resulted in a high induction of SCEs. It was also shown for heliotrine that co-cultivation with chick embryo hepatocytes resulted in a much higher response than addition of activated rat-liver homogenate to the test medium.

Four alkaloids, ligularizine, senkirkine and senecionine N-oxide, were isolated from S. gallicus. Apart from florosenine, a new alkaloid was isolated from S. adonidifolius and identified as 12,13,19-trihydroxy-15,20-epoxy-15,20-dihydro(12S,15R,20R senecionan-11,16-dione. Two dimensional spectroscopic correlation experiments (1H1H and 13C1H) were performed, permitting the unequivocal assignation of the 1H and 13C NMR spectra of the alkaloids and enabling us to correct some of the data appearing in the literature.

Seneciphylline and senkirkine, two pyrrolizidine alkaloids that occur in animal feeds and medicinal herbs, respectively, have been tested for their ability to produce sex-linked recessive lethals in males of Drosophila melanogaster using the Basc test (3-day feeding method). Seneciphylline was found to be mutagenic at concentrations of 10−5, 10−4 and 10−3 m , which produced 3.8% sex-linked recessive lethals (983 chromosomes tested), 9.0% (708) and 15.3% (327), respectively. Senkirkine (10−5 m ) produced 4.4% sex-linked recessive lethals (2541 chromosomes tested) against 0.17% (9081) in controls. Brood pattern analysis with senkirkine showed maximum sensitivity in the late spermatid stage of spermatogenesis, which agrees with evidence that pyrrolizidine alkaloids act as indirect mutagens. Flies fed with milk from lactating rats given an oral dose of 25 mg seneciphylline/kg showed 1.2% sex-linked recessive lethals (1477 chromosomes tested), against 0.3% (1533) in controls.

The pyrrolizidine alkaloids, senkirkine ( 1) and doronine ( 2) were isolated from the aerial parts of EMILIA SONCHIFOLIA.

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 derivatives2,3 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.

NEWBORN rats have proved strikingly more susceptible than weanlings to the hepatotoxic action of a single dose of the hepatocarcinogen retrorsine, and also to senkirkine and hydroxysenkirkine (cyclic diesters of otonecine). It is usually accepted that substances which induce principally liver tumours require “activation” by liver microsomal enzymes before they become “proximal” (locally acting) carcinogens. Newborn rats, however, are deficient in enzymes which metabolize drugs, but they are very susceptible to hepatocarcinogens. My work has led me to suggest that the “activated” species of pyrrolizidine alkaloids, aflatoxins and certain other carcinogens are the respective epoxides formed on their chemically reactive double bonds. The microsomal enzymes present in older rats probably accelerate the conversion of the epoxides into less active forms.

The medicinal herb, Tussilago farfara L., is shown to contain the hepatotoxic pyrrolizidine alkaloid, senkirkine.

Two pyrrolizidine alkaloids, neosenkirkine and senkirkine were isolated from the roots and aerial parts of Senecio pierotii. As part of the screening for carcinogenic pyrrolizidine alkaloids in the Boraginaceae and Compositae, two pyrrolizidine alkaloids, neosenkirkine and senkirkine were isolated from the roots and aerial parts of Senecio pierotii (Compositae, Japanese name: Sawaoguruma), whose young plants are used as foods for men in two or three rural areas in Japan. The MeOH extract of the dried roots (600 g), collected in Aizu district of Fukushima Prefecture during flowering from 1979 to 1981, was extracted with 0.5N H2SO4. The acid soluble fraction was extracted with Et2O, the acidic solution was made alkaline with ammonia and extracted with CHC13. The CHC13 solution was evaporated to give a crude alkaloidal mixture (1.08 g). This was chromatographed over aluminum oxide column and the mixture of Alkaloid I and Alkaloid II was carefully separated by HPLC to give neosenkirkine I (3.2 mg) and senkirkine II (25.5 mg). The extraction procedure of alkaloid from the aerial parts (2.1 kg) was carried out by the same method as described above. Neosenkirkine and senkirkine were obtained in crystalline. This is the second occasion in which neosenkirkine has been found in nature; senkirkine has been found in several plant species [2-4]. Alkaloid I: m.p. 216° (n-hexane), [a]D 4 + 26.8° (CHC13), (Found: M, 365.1853 C19H27O6N requires: M , 365.1838), IR vTM cm: 3360, 1735, 1705, 1600, NMR

Crotalaria laburnifolia L. subsp. eldomae has been found to contain anacrotine (I), its isomer madurensine (II), and senkirkine (III), together with two new alkaloids, crotafoline (V) and hydroxysenkirkine (IV).