AdvisorHixtable, Ryan J.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractTylophora sylvatica is a medicinal plant successfully used in African folk medicine for the management of various allergic conditions. This plant was investigated using screening methods suitable for the isolation of the active constituents which inhibit the release of chemical mediators of allergic reactions. Chromatographic studies led to the characterization of two classes of active principles: known fatty acids (oleic, linoleic and linolenic acids) with 0.064% yield; two novel glycosides, tylophoroside and acetyltylophoroside, having 0.008% and 0.0113% yields, respectively. Mild acidic hydrolysis of these glycosides generated an aglycone termed tylogenin which appears to be a biodegraded steroid. The antiallergic activity of these compounds was further assessed for inhibition of antigen-induced mediator release by the rabbit basophil-dependent serotonin release(B08R) and human leukocyte-dependent histamine release(LDHR) assay systems. The activity of tylogenin was found to increase with the incubation time. In the B08R assay, at optimal incubation time, tylogenin with a geom mean IC₅₀ of 38.9 μM, (geom SD=1.3, n=5), exhibited an activity similar to that of the fatty acids. This activity differed significantly (p<0.05) from that of the standard corticosteroids, dexamethasone (geom mean IC50=912 μM, geom 80=2.8, n=5) and prednisolone (geom mean IC₅₀=1071.5 μM, geom 80=3.2, n=4). In the LOHR assay, the activity of tylogenin (geom mean IC₅₀=49.0 μM, geom 80=1.6, n=5) significantly exceeded that of dexamethasone (geom mean IC₅₀=257 μM geom 80=8.1), (p<0.05). Tylophora compounds were also investigated for a potential cardiac activity based on their structural similarity with cardiac glycosides. In the Na+/K+ ATPase assay, Tylophora compounds displayed a dose-dependent inhibitory activity of the sodium pump enzyme. However, these compounds were 100 times less active than ouabain (gem meanIC₅₀=2.3 μM, geom SD=1.4, n=5). Additional studies indicated that the standard cardenolides had no antiallergic activity at concentrations ranging from 0.1 nM to 300 μM, and standard corticosteroids had no ATPase inhibitory activity. Thus, Tylophora compounds were shown to possess an apparently unique dual activities. These compounds were also found to be devoid of cytotoxicity by dye exclusion and may represent a new class of agents with dual antiallergic and cardiac activities.
Degree ProgramPharmacology and Toxicology