Asclepias, cardenolides

Groeneveld, H., van den Berg, B., Elings, J. and Seykens, D. (1990) Cardenolide biosynthesis from malonate in Asclepias curassavica. Phytochemistry, 29,3479-86. 

Warashina, T. and Noro, T. (2000) Cardenolide and oxypregnane glycosides from the root of Asclepias incarnata L. Chem. Pharm. Bull., 48,516-24. 

Asclepias tuberosa (plenrisy root) contains cardenolides snch as nzarigenin, coroglancigenin, and corotoxigenin. 

Asclepias fruticosa L. [lubetjane, milkweed] (Asclepiadaceae) stem bark concoction is used in the treatment of asthma. The stem bark contains alkaloids, flavonoids, polyphenols, saponins and steroids (15). The aerial parts contain cardenolides (55). The powdered leaf is used as a snuff for the treatment of pulmonary tuberculosis, producing violent and prolonged sneezing in the process (28). 

The cardenolides of the Asclepiadaceae differ from those of the Apocynaceae and the Scrophulariaceae, in that the former have a 5cL trans A/B) and the latter a 5(3(cw A/B) ring junction. The latter type is useful clinically in humans, whereas the former normally is not (Seiber et al., 1984). At least 30% of the cardiac glycosides of young plants of Asclepias curassavica occurs in the latex (Groeneveld et al., 1991). 

Despite the fact that cardenolides usually are described as bitter tasting, milkweed poisoning in livestock is a persistent problem. Normally, animals will not eat the apparently distasteful plants, but in time of scarcity, many animals (especially sheep) succumb to this type of poisoning (Malcolm, 1991 Seiber et al., 1984). As little as 0.8 oz. of dry Asclepias labriformis leaf is fatal to a 100-lb sheep (Harbome, 1991). 

Over its natural range in North America, the female monarch butterfly may lay her eggs on several Asclepias species that differ in the complement and amount of cardenolides present. By TLC analysis of adult butterflies, it is possible to determine the species upon which the larva feed. Depending on the complement and quantity of cardenolides present in the host plant, the larvae are able to adjust their diet to modify the amount of cardenolide sequestered (Harbome, 1991). 

Groeneveld, H. W., H. Stedl, B. van der Berg, and J. C. Elings, Rapid, quantitative HPLC analysis of Asclepias fruticosa L. and Danaus plexippus L. cardenolides, J. Chem. Ecol., 16, 3373-3382 (1990). 

Groeneveld, H. W., A. Binnekamp, and D. Seykens, Cardenolide biosynthesis from acetate in Asclepias curassavica. Phytochemistry, 30, 2577-2585 (1991). 

Lee, S. M. and J. N. Seiber, Biosynthetic preparation of cardenolides from [l- C]acetic acid by stem discs of the milkweed Asclepias curassavica, Ph3dochemistry, 22, 923-927 (1983). 

Malcolm, S. B., B. J. Cockrell, and L. P. Brower, Cardenolide fingerprint of monarch butterflies reared on common milkweed, Asclepias syriaca L., J. Chem. Ecol., 15, 819-853 (1989). 

Martin, R, A. and S. P. Lynch, Cardenolide content and thin-layer chromatography profiles of monarch butterflies, Danaus plexippus L., and their larval host-plant milkweed, Asclepias asperula subsp. capricornu (Woods.) Woods., in North Central Texas, J. Chem. Ecol., 14, 295-318 (1988). 

Brower, L.P., J.N. Seiber, C.J. Nelson, S.P. Lynch, and N.N. Holland Plant Determined Variation in the Cardenolide Content, Thin-Layer Chromatography Profiles and Emetic Potency of Monarch Butterflies, Danaus plexippus L. Reared on Milkweed Plants in California. 2. Asclepias speciosa. J. Chem. Ecol. 10, 601-639 (1984). 

Brower, L. P., Seiber, J. N., Nelson, C. J., Lynch, S. P. andTuskes, P. M. (1982)Plant-determined variation in the cardenolide content, thin-layer chromatography profiles, and emetic potency of monarch butterflies, Danaus plexippus, reared on the milkweed, Asclepias eriocarpa, in California. J. Chem. Ecol., 8, 579-633. 

Isman, M. B., Duffey, S. S. and Scudder, G. G. E. (1977) Cardenolide content of some leaf- and stem-feeding insects on temperate North American milkweeds (Asclepias spp.). Can. J. ZooL, 55, 1024-8. 

Recent studies on Asclepias curassavica [197], and Bersama abyssinica [198, 199] have shown that bufadienolides and cardenolides are cytotoxic and that hellebrigenin 3-acetate (XLIX) inhibits W 256 at 8 mg/kg. Structure-activity relationship studies on bufadienolides and cardenolides have failed to reveal the structural features required for activity [194]. 

A doubly linked 4,6-dideoxy-D-j/ rgo-hexos-2-ulose residue was identified in the cardenolide glycoside (1) isolated from Asclepias curassavica stems, and a branched hexos-4-ulose derivative isolated from Pittosporum tobira flowers is covered in Chapter 14. Oxidation (MCPBAAleOH) of unsaturated derivative (2) (obtained by base treatment of methyl 3,4-0-isopropylidene-2,6-di-0-methyl-P-D-galactopyranoside) afforded L-arabino-hexos-S-ulose derivative (3) and then (4) after acid hydrolysis. The hexopyranosid-3-uloses (5) have been prepared by oxidation (Cr03/Ac20/pyridine) of the corresponding 3-alcohols. ... 

There are several research observations which support the utilization of cardenolides in milkweed by monarch butterflies for purposes of defense. First, the monarch larvae feed exclusively on species of Asclepias through all developmental stages (Urquhart, 1960). Second, the insects are capable of selective storage of some cardenolides among different members of Asclepiadaceae (Roeske et al., 1976 Brower et al., 1982). Finally, metabolic conversion to specific types of cardenolides occurs in the monarch (Seiber et al., 1980). These data and the emetic response ellicited by the cardenolides in vertebrates provide compelling evidence on behalf of the utilization of phytochemicals by insects for the purpose of defense against predators. 

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