Alkaloids from the Poisonous Plant Ipomoea carnea:  Effects on Intracellular Lysosomal Glycosidase Activities in Human Lymphoblast Cultures

There is natural intoxication of livestock by the ingestion of Ipomoea carnea (Convolvulaceae) in Brazil 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 IC50 values of 2.1, 0.75, and 0.84 μM, respectively. The action of swainsonine results in a lysosomal storage disorder that closely mimics α-mannosidosis in humans. To determine whether the toxicity of I. carnea to livestock is due to purely swainsonine or due to a combination of effects by swainsonine and calystegines, intracellular lysosomal glycosidase activities in normal human lymphoblasts grown with inhibitors in the medium were examined. Incubation of lymphoblasts with 0.1 μM swainsonine for 3 days resulted in ∼60% reduction of α-mannosidase activity. On the other hand, calystegines B2 and C1 showed no inhibition of β-glucosidase up to 1 mM; instead inclusion of calystegines B2 and C1 at 100 μM in the culture medium increased its activity by 1.5- and 1.6-fold, respectively. Calystegines B2 and C1 seem to act as chemical chaperones, enhancing correct folding of the enzyme and enabling smooth trafficking to the lysosome. The lysosomal β-glucosidase inhibitory calystegines seem to have little risk of inducing intoxication of livestock. Keywords: Ipomoea carnea; toxic principle; swainsonine; calystegine; human lymphoblast