Abstract
| - There is natural intoxication of livestock by the ingestion of Ipomoea carnea (Convolvulaceae) inBrazil and other parts of the world. The alkaloidal glycosidase inhibitors swainsonine, 2-epi-lentiginosine, and calystegines B1, B2, B3, and C1 have been identified as constituents of this plant.Swainsonine is a potent inhibitor of rat lysosomal α-mannosidase, with an IC50 value of 0.02 μM,whereas calystegines B1, B2, and C1 are potent inhibitors of rat lysosomal β-glucosidase, with IC50values of 2.1, 0.75, and 0.84 μM, respectively. The action of swainsonine results in a lysosomalstorage disorder that closely mimics α-mannosidosis in humans. To determine whether the toxicityof I. carnea to livestock is due to purely swainsonine or due to a combination of effects by swainsonineand calystegines, intracellular lysosomal glycosidase activities in normal human lymphoblasts grownwith inhibitors in the medium were examined. Incubation of lymphoblasts with 0.1 μM swainsoninefor 3 days resulted in ∼60% reduction of α-mannosidase activity. On the other hand, calystegines B2and C1 showed no inhibition of β-glucosidase up to 1 mM; instead inclusion of calystegines B2 andC1 at 100 μM in the culture medium increased its activity by 1.5- and 1.6-fold, respectively. CalysteginesB2 and C1 seem to act as chemical chaperones, enhancing correct folding of the enzyme and enablingsmooth trafficking to the lysosome. The lysosomal β-glucosidase inhibitory calystegines seem to havelittle risk of inducing intoxication of livestock. Keywords: Ipomoea carnea; toxic principle; swainsonine; calystegine; human lymphoblast
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