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PubMed1997

The role of constitutive and inducible nitric oxide synthase in senna- and cascara-induced diarrhoea in the rat.

The role of constitutive and inducible nitric oxide (NO) synthase in rats treated with senna and cascara was studied. Senna (60 mg/kg p.o.) and cascara (800 mg/kg p.o.) ex vivo significantly increased Ca(2+)-dependent constitutive NO synthase activity in the rat colon. Induction of NO synthase (12% of the total NO synthase) was associated with cascara, but not senna, administration. Dexamethasone (0.03-0.3 mg/kg i.p.), which inhibits the expression of inducible NO synthase, significantly and dose-dependently reduced cascara-(but not senna-) induced diarrhoea and colonic fluid secretion. These findings suggest that senna probably exerts its laxative effect through stimulation of the constitutive isoform of NO synthase, while the inducible isoform of NO synthase also seems to be involved in the laxative effect of cascara.

Administration, Oral↗
PubMed1988

Preliminary applications of cross-axis synchronous flow-through coil planet centrifuge for large-scale preparative counter-current chromatography.

The cross-axis synchronous flow-through coil planet centrifuge with a 20-cm revolutional radius and a total capacity of 1600 ml was successfully applied to preparative counter-current chromatography of various biological samples, which include sea buckthorn extract, steroid reaction mixture, indole plant hormones, and dinitrophenylamino acids. The present system offers advantages of stable balance of the centrifuge, a large column capacity, and high resolution.

Amino Acids↗
PubMed1990

Improved high-speed counter-current chromatograph with three multilayer coils connected in series. II. Separation of various biological samples with a semi-preparative column.

The semipreparative capability of the newly developed high-speed counter-current chromatograph equipped with a set of three multilayer coils has been demonstrated in separations of a variety of biological samples including triterpenoic acids, indole auxins, bacitracin, flavonoids and tetracycline derivatives, each with a suitable two-phase solvent system. The sample quantities ranging from 50 to 500 mg were efficiently separated within a few hours. The separation of tetracycline derivatives was remarkably improved by adding ammonium acetate to the solvent system.

Bacitracin↗
PubMed1998

Clinical diagnosis in Karwinskia humboldtiana polyneuropathy.

Intoxication by Karwinskia humboldtiana presents a neurological picture similar to that for Guillain-Barré syndrome or other polyradiculoneuropathies. Clinical diagnosis in poisoned humans may be difficult if no evidence of previous fruit ingestion is available. We present our experience in the clinical diagnosis of Karwinskia humboldtiana polyneuropathy, as confirmed by toxin detection in blood. We designed an open trial at the Pediatric Neurology service and included all cases with acute ascending paralysis that were admitted to our hospital in the last two years. In all cases, we performed hematological, immunological and biochemical profiles, CSF analysis including immunological studies, oligoclonal bands and myelin basic protein determinations. Electrodiagnostic studies were performed, including motor conduction velocities, distal latencies, F-wave latency and compound muscle action potential (CAMP) amplitude. The presence of Karwinskia humboldtiana toxins in blood were determined by thin layer chromatography. In six cases, T-514 Karwinskia humboldtiana toxin was detected. These cases had a symmetric motor polyneuropathy with the absence of tendon reflexes and no sensory signs or cranial nerve involvement. Only one patient required assisted ventilation due to bulbar paralysis. In two of these cases, a sural nerve biopsy revealed a segmental demyelination with swelling and phagocytic chambers in Schwann cells and without lymphocytic infiltration. All six cases survived, with complete recovery in five. We conclude that this intoxication is common in Mexico. The availability of toxin detection in blood samples allows the clinician to establish an accurate diagnosis and should be included in the study of children with polyradiculoneuropathy, especially in countries where this poisonous plant grows.

Child↗
PubMed2001

Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon.

Laxatives abuse has been associated with an increased risk for colon cancer. However, little is known about laxatives long-term carcinogenic potential in experimental studies. The present study was designed to investigate the effects of bisacodyl (4.3 and 43 mg/kg) and cascara (140 and 420 mg/kg) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors. Animals, divided in 10 groups were treated with AOM and laxatives (alone or in combination) for 13 weeks. At the end of treatment animals were killed and the colon removed and analysed for the determination of ACF and tumors. Bisacodyl (4.3 and 43 mg/kg), given alone, did not induce the development of colonic ACF and tumors. Bisacodyl (4.3 mg/kg) coupled with AOM increased the number of crypt per focus, but not the number of tumors. Bisacodyl (43 mg/kg) significantly increased the number of crypt per focus and tumors. Cascara (140 and 420 mg/kg) did not induce the development of colonic ACF and tumors and did not modify the number of AOM-induced ACF and tumors. The results of the present study indicate a possible promoting effect of bisacodyl on rat colon carcinogenesis (especially at higher doses) and absence of any promoting or initiating activity of a laxative and diarrhoeal dose of cascara.

Adenocarcinoma↗
PubMed1999

Biologically active anthracenones from roots of Karwinskia parvifolia.

Tullidinol, a neurotoxin isolated from fruits and roots of several Karwinskia species, was resolved for the first time into two stereoisomers. This was achieved by means of preparative HPLC from roots of Karwinskia parvifolia. Structural assignments were made on the basis of spectroscopic data, including long range correlations as well as geometry optimization by means of semi-empirical methods.

Animals↗
PubMed2003

Heavy metals in the dump of an abandoned mine in Galicia (NW Spain) and in the spontaneously occurring vegetation.

The concentrations of different forms of heavy metals (Fe, Mn, Zn, Cu, Cr, Ni, Cd and Pb) were determined in a mine dump material rich in chalcopyrite. The concentrations were compared with those of the natural vegetation colonising the dump. Samples taken from the dump are acid (pH(H(2)O) between 3.0 and 5.0), have carbon contents lower than 0.5%, N lower than 0.2%, effective cation exchange capacity between 0.74 and 4.96 cmol(+)kg(-1) and percent Al saturation in the exchange complex higher than 20% in 85% of the samples. Iron was the most abundant heavy metal, in both total and bioavailable forms, and the relative abundance of metals was: Fe>Cu>Mn>Zn>Cr. The total Fe concentrations ranged between 4315 and 31578 mg x kg(-1), the total Cu between 273 and 5241 mg x kg(-1), the total Mn between 294 and 2105 mg x kg(-1), the total Zn between 73 and 894 mg x kg(-1) and total Cr between 0.01 and 30 mg x kg(-1). Ni, Cd and Pb were below the analytical detection limits. The concentration of bioavailable Fe ranged between 40 and 1550 mg x kg(-1); Zn was the least abundant metal in this fraction (between 2 and 100 mg x kg(-1)). Copper was the most abundant heavy metal in the exchange complex and in the aqueous extracts, followed by Zn, Mn and Fe. Exchangeable Cu ranged between 17.7 and 1866 mg x kg(-1), whereas the maximum concentrations of exchangeable Zn, Mn and Fe did not exceed 140 mg x kg(-1). The Cu concentration in the aqueous extracts varied between 0.1 and 8.3 mg x l(-1) and the concentration of Fe was always less than 0.52 mg x l(-1). The heavy metal contents in the spontaneously occurring vegetation in the dump ranged between: 150 and 900 mg Fe x kg(-1), 84 and 2069 mg Mn x kg(-1), 20.5 and 106 mg Cu x kg(-1) and between 35 and 717 mg Zn x kg(-1), when considering all the plant samples analysed. Festuca sp. accumulated Fe, Salix atrocinerea accumulated Zn and Mn, and Frangula alnus and Quercus robur accumulated Mn. These native plant species may contribute to decrease the heavy metal contents in the dump material.

Environmental Monitoring↗
PubMed2001

Cyclopeptide alkaloids from Zizyphus jujuba.

A new cyclopeptide alkaloid, jubanine-C (1), together with known alkaloids scutianine-C (4) and zizyphine-A (5), have been isolated from the stem bark of Zizyphus jujuba and identified by spectral analysis.

Alkaloids↗
PubMed1999

High-performance liquid chromatographic determination of peroxisomicine A1 (T-514) in genus Karwinskia.

A chromatographic method was developed for the T-514 determination in Karwinskia leaves, stems and roots. A C18 analytical column and a mobile phase consisting of methanol and McIlvaine buffer (pH 3) were used. T-514 was detected using a diode array detector and the chromatograms were recorded at 269 and 410 nm. A linear dependence of a peak area on the T-514 concentration (r=0.9991) was obtained in the range of 0.126-12.6 microg/ml. Limits of T-514 quantification (signal-to-noise ratio 10) in plant samples were 126 ng/ml at 410 nm and 28 ng/ml at 269 nm. T-514 was extracted from the plant material with ethyl acetate. Optimal extraction conditions were studied: number of extraction steps, volume of extracting agent and extraction time. The extracts were cleaned up using solid-phase extraction (SPE). SPE recoveries of 99.9% and 98.4% were achieved for the T-514 concentrations of 1.4 microg/ml and 0.26 microg/ml, respectively.

Anthracenes↗
PubMed1999

Review article: anthranoid laxatives and their potential carcinogenic effects.

Anthranoid laxatives are widely used laxatives of natural origin. Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place. These aglycones exert their laxative effect by damaging epithelial cells, which leads directly and indirectly to changes in absorption, secretion and motility. Damaged epithelial cells can be found as apoptotic bodies in the pigmented colonic mucosa, characteristic for pseudomelanosis coli. Pseudomelanosis coli is a condition caused by chronic (ab)use of anthranoid laxatives and has recently been associated with an increased risk of colorectal carcinoma. In vitro and animal studies have shown a potential role of anthranoid laxatives in both the initiation and promotion of tumorigenesis. Studies in humans have also suggested tumour promoting activities for these laxatives. Although the short-term use of these substances is generally safe, long-term use cannot be recommended.

Animals↗
PubMed2003

Rangewide phylogeography of a bird-dispersed Eurasian shrub: contrasting Mediterranean and temperate glacial refugia.

We studied the phylogeography of alder buckthorn (Frangula alnus), a bird-dispersed shrub or small tree distributed over most of Europe and West Asia and present in three of the four main refugia of West Palaearctic temperate woody plants: the Iberian Peninsula, the Balkans and Anatolia. A total of 78 populations from 21 countries were analysed for chloroplast DNA variation using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and 21 different haplotypes were distinguished. We found a very strong overall population differentiation (GST = 0.81) and phylogeographical structure, and a sharp contrast between the haplotype-rich refugia and the almost completely uniform area of postglacial colonization. The haplotype network comprises three lineages made up of haplotypes from the Iberian Peninsula, Anatolia with the Caucasus, and temperate Europe. The Iberian and the Anatolian branches represent parts of a major lineage that spans over the whole northern Mediterranean Basin and some neighbouring areas and probably dates back to the Tertiary. Many haplotypes of this lineage are distributed locally and most populations are fixed for a single haplotype; these populations have apparently been very stable since their establishment, experiencing negligible gene flow and few mutations. The temperate European lineage consists of one very widespread and abundant plus six locally distributed haplotypes. Four of them are located in Southeast Europe, the putative refugium of all extant temperate European populations. Contrary to populations from Iberia and Anatolia, F. alnus populations from the southeastern European refugium have most genetic variation within populations. Bird-mediated seed dispersal has apparently allowed not only a very rapid postglacial expansion of F. alnus but also subsequent regular seed exchanges between populations of the largely continuous species range in temperate Europe. In contrast, the disjunct F. alnus populations persisting in Mediterranean mountain ranges seem to have experienced little gene flow and have therefore accumulated a high degree of differentiation, even at short distances. Populations from the southern parts of the glacial refugia have contributed little to the postglacial recolonization of Europe, but their long-term historical continuity has allowed them to maintain a unique store of genetic variation.

DNA, Chloroplast↗
PubMed1999

2'-carboxy-D-arabitinol 1-phosphate protects ribulose 1, 5-bisphosphate carboxylase/oxygenase against proteolytic breakdown.

Trypsin-catalysed cleavage of purified ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and the resultant irreversible loss of carboxylase activity were prevented by prior incubation with the naturally occurring nocturnal Rubisco inhibitor 2'-carboxy-D-arabitinol 1-phosphate (CA1P), as well as with ribulose 1,5-bisphosphate (RuBP), Mg2+ and CO2. CA1P also protected Rubisco from loss of activity caused by carboxypeptidase A. When similar experiments were carried out using soluble chloroplast proteases, CA1P was again able to protect Rubisco against proteolytic degradation and the consequent irreversible loss of catalytic activity. Thus, CA1P prevents the proteolytic breakdown of Rubisco by endogenous and exogenous proteases. In this way, CA1P may affect the amounts of Rubisco protein available for photosynthetic CO2 assimilation. Rubisco turnover (in the presence of RuBP, Mg2+ and CO2) may confer similar protection against proteases in the light.

Carboxypeptidases↗
PubMed1991

Bicascarosides in fluid extracts of cascara.

Bianthraquinone glycosides are formed during the preparation and conservation of fluid extracts of cascara. Analysis of these preparations has shown that up to 20% of total amount of anthracene glycosides can be dimerized. These dimers are devoid of laxative activity. They are absorbed in the intestine and very slowly excreted.

Animals↗
PubMed2001

Cytotoxic hydroxyanthracenones from fruits of Karwinskia parvifolia.

Peroxisomicines A1 (1) and A2 (2) are cytotoxic hydroxyanthracenones isolated from the fruits of Karwinskia parvifolia. Peroxisomicine A1 exhibits selective cytotoxicity against several tumor cell lines. In the present investigation three minor constituents were obtained from the same fruit extracts: peroxisomicine A3 (3) and isoperoxisomicines A1 (4) and A2 (5). Compounds 3 and 5 are novel and their structures were determined by spectroscopic methods and molecular modeling. Compounds 1-5 were significantly cytotoxic against hepatoma cell lines.

Anthracenes↗
PubMed1996

Genotoxic effects of Karwinskia humboldtiana toxin T-514 in peripheral blood lymphocytes.

Toxicity by Karwinskia humboldtiana, a Rhamnaceae plant, has been assessed in a number of studies. Four dimmeric anthracenones, named T-496, T-514, T-516 and T-544 for their molecular weight, have been isolated from this plant. T-514, in particular, has been shown to be toxic to liver and lung as well as to tumoral cell lines, preferentially to those from liver tumors. For this reason it has been suggested that the toxin could be used as an antineoplastic agent. The present study was performed to characterize the biological activity of T-514 as a potential cytostatic and genotoxic agent. Peripheral blood lymphocytes in culture were used as a test system, where chromosomal aberrations and sister chromatid exchanges were scored in order to evaluate genotoxicity, and mitotic index and cell proliferation kinetics were used as parameters for cytostatic and cytotoxic ability. Genotoxicity to lymphocytes was negative. However, proliferation was affected by the toxin, demonstrating a cytostatic activity independent of genotoxic damage.

Adult↗
PubMed2000

Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity.

Herbal medicines are gaining widespread popularity. Much of the public believes that botanical herbs are both harmless and useful for the treatment of a variety of symptoms. This belief stands in contrast with the fact that many herbal therapies have been shown to be toxic. In the present case report, cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension. CS is a mixture of ingredients, among which is anthracene glycoside--an herbal agent that previously has been associated with chronic hepatitis. The liver injury in the case herein reported is believed to be related to either anthracene glycoside or one of the other constituents of CS.

Biopsy↗