piperidines and ammodendrine

The aim of current research was to evaluate the physiological adjustment in three medicinal herbs viz., Atropa acuminata, Lupinus polyphyllus and Hyoscyamus niger to the winter period characterised by intense UV flux in Kashmir valley across the North Western Himalaya. Quinolizidine (QA) and tropane alkaloid (TA) concentrations were analysed in these herbs thriving at two different altitudes via GC-MS and correlated by PCA analysis. This study investigated the hypothesis that UV reflectance and absorbance at low temperatures are directly related to disparity in alkaloid accumulation. Among QAs in L. polyphyllus, ammodendrine and lupanine accumulated at higher concentration and exhibited significant variation of 186.36% and 95.91% in ammodendrine and lupanine respectively in both sites. Tetrahydrohombifoline displayed non-significant variation of about 9.60% irrespective of sites. Among tropane alkaloid (TA), hyoscyamine was recorded as the most abundant constituent irrespective of the plant and site while apotropine accumulated in lesser quantity in A. acuminata than H. niger. However, apotropine demonstrated significant variation of 175% among both sites. The final concentration of quinolizidine (QA) and tropane alkaloid (TA) reflects the interplay between reflectance and absorbance of UV radiation response field. These findings suggest that spectral response of UV light contributes directly to alkaloid biosynthesis.

Topics: Alkaloids; Atropa; Gas Chromatography-Mass Spectrometry; Hyoscyamus; Lupinus; Piperidines; Plant Extracts; Plant Leaves; Principal Component Analysis; Pyridines; Quinolizidines; Sparteine; Temperature; Tropanes; Ultraviolet Rays

Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly crooked calf disease in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primarily responsible for crooked calf disease. Lupines also contain teratogenic piperidine alkaloids including ammodendrine. Previous work in sheep has shown that lupine alkaloid clearance may be influenced by the animal's physiological status. Therefore, the purpose of this study was to determine if differences in body condition of cattle would alter the absorption and elimination of anagyrine or ammodendrine given in a single oral dose as Lupinus leucophyllus or Lupinus sulphureus, respectively. Mature non-lactating cows in low body condition (LBC, n = 4) and high body condition (HBC, n = 4) received a single dose of dry ground lupine plant (2.0 g/kg of BW) via oral gavage. Lupinus leucophyllus (anagyrine) was dosed first; then after 21 d the same animals were dosed with L. sulphureus (ammodendrine). Blood samples were taken via jugular venipuncture 0 to 60 h after dosing. Serum anagyrine and ammodendrine concentrations were evaluated. The concentration of anagyrine was greater (P = 0.001) in the HBC group and peaked 2 h after dosing versus 12 h in LBC cows. Similarly for ammodendrine, the alkaloid concentration peaked at 3 h after dosing for the HBC group compared with 6 h for the LBC group (P = 0.001). Area under the curve tended to differ (P

Topics: Alkaloids; Animals; Azocines; Cattle; Cattle Diseases; Female; Health Status; Lupinus; Piperidines; Pyridines; Quinolizines

Ammodendrine (1) was found to occur as a mixture of enantiomers in two different collections of plants identified as Lupinus formosus. The ammodendrine fraction was reacted in a peptide coupling reaction with 9-fluorenylmethoxycarbonyl-L-alanine (Fmoc-L-Ala-OH) to give diastereomers, which were separated by preparative HPLC. The pure D- and L-ammodendrine enantiomers were then obtained by Edman degradation. Optical rotation measurements revealed that the D- and L-enantiomers had optical rotations of [alpha]24D +5.4 and -5.7, respectively. D- and L-N-methylammodendrine enantiomers were synthesized from the corresponding ammodendrine enantiomers, and their optical rotations established as [alpha]23D +62.4 and -59.0, respectively. A mouse bioassay was used to determine the difference in toxicity between these two pairs of naturally occurring enantiomers. The LD50 of (+)-D-ammodendrine in mice was determined to be 94.1 +/- 7 mg/kg and that of (-)-L-ammodendrine as 115.0 +/- 7 mg/kg. The LD50 of (+)-D-N-methylammodendrine in mice was estimated to be 56.3 mg/kg, while that of (-)-L-N-methylammodendrine was determined to be 63.4 +/- 5 mg/kg. These results establish the rotation values for pure ammodendrine and N-methylammodendrine and indicate that there is little difference in acute murine toxicity between the respective enantiomers.

Topics: Animals; Cattle; Cattle Diseases; Chromatography, High Pressure Liquid; Dihydropyridines; Disease Models, Animal; Lupinus; Mice; Molecular Structure; Piperidines; Plants, Edible; Pyridines; Stereoisomerism

Cleft palate and minor front limb contractures were induced in calves by maternal ingestion of the piperidine alkaloid-containing lupines, Lupinus formosus and L. arbustus. Crooked calf disease, which includes an occasional cleft palate, is a congenital condition of widespread occurrence in cattle in the western U.S. and Canada. It is known to occur after maternal ingestion of certain species of Lupinus during specific gestational periods. Although many lupine species contain quinolizidine alkaloids including the teratogenic alkaloid anagyrine, L. formosus and L. arbustus produce piperidine alkaloids including the reported teratogen ammodendrine. In addition to ammodendrine, L. formosus contains both N-acetyl hystrine and N-methyl ammodendrine, whereas L. arbustus contains ammodendrine, trace amounts of N-methyl ammodendrine, and no N-acetyl hystrine. L. formosus and L. arbustus were fed to pregnant cows at equivalent ammodendrine doses during a 10-day period from days 40-50 of gestation. One calf from a cow fed L. formosus had a full cleft palate. Embryonic death and resorption of one fetus and minor front limb contractures (arthrogryposis) in another calf occurred with two cows fed L. arbustus. Alkaloid analysis of blood samples taken during the feeding period, and up to and including 48 hours after the last dose, demonstrated comparative plasma elimination times with N-methyl ammodendrine > ammodendrine > N-acetyl hystrine. The objectives of this experiment were to: 1) determine if N-acetyl hystrine is a potential teratogen; and 2) define the narrow cleft palate induction period in cows.

Topics: Alkaloids; Animal Feed; Animals; Arthrogryposis; California; Cattle; Cattle Diseases; Cleft Palate; Dihydropyridines; Female; Fetal Death; Gestational Age; Idaho; Piperidines; Plants, Toxic; Pregnancy; Prenatal Exposure Delayed Effects; Pyridines; Structure-Activity Relationship; Teratogens

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

Topics: Abnormalities, Multiple; Alkaloids; Anabasine; Animals; Bone and Bones; Cleft Palate; Female; Goat Diseases; Goats; Nicotiana; Piperidines; Plant Extracts; Plant Poisoning; Plants, Toxic; Pregnancy; Pyridines; Teratogens