tenulin and hymenovin

The sesquiterpene lactones isolated from Geigeria were found to be incapable of inducing rat peritoneal mast cell degranulation at levels of 0.3-1.6 mM. The sulphydryl reagent, N-ethylmaleimide, too was unable to trigger mast cell secretion. Instead, it was observed that these compounds inhibited the release of histamine induced by Compound 48/80. Pretreatment of the lactones and N-ethylmaleimide with the amino acid, L-cysteine, reduced their inhibition ability of histamine release to a considerable extent, but not completely. Geigerin(V), which lacks an alpha-methylene group and the chemically prepared cysteine-adduct of dihydrogriesenin(I), were also capable of inhibiting mast cell secretion by Compound 48/80, but to a lesser extent.

Topics: Alkylation; Animals; Cysteine; Ethylmaleimide; Histamine Release; Lactones; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Plant Extracts; Rats; Rats, Inbred Strains; Sesquiterpenes; Sesquiterpenes, Guaiane; Thapsigargin

Inhibition of murine macrophage adenylate cyclase activity by sesquiterpene lactones isolated from toxic forage plants was highly correlated with the presence of the alpha-methylene-gamma-lactone moiety on the molecule (ie, hymenovin and helenalin). Tenulin, a sesquiterpene lactone which does not contain this reactive moiety, caused minimal inhibition of the enzyme. Reaction of the alpha-methylene-gamma-lactone moiety of hymenovin and helenalin with cysteine decreased the number of reactive moieties available to alkylate the enzyme, thus decreasing the inhibition of adenylate cyclase by these 2 sesquiterpene lactones. As the reaction time available for the reduction by cysteine of the alpha-methylene-gamma-lactone moiety decreases, the amount of adenylate cyclase inhibition increases. Stimulation of the hymenovin- or helenalin-inhibited adenylate cyclase by prostaglandin E1 or E2 or by sodium fluoride did not reverse the inhibition of the enzyme, but did stimulate the undamaged adenylate cyclase in the sesquiterpene lactone treatment groups to the same degree as in the nontreated control. These data indicate that sesquiterpene lactones containing an alpha-methylene-gamma-lactone moiety are potent inhibitors of macrophage adenylate cyclase activity. This moiety may have a significant role in the toxicity of some sesquiterpene lactones in poisonous plants when ingested by livestock.

Topics: Adenylyl Cyclase Inhibitors; Animal Feed; Animals; In Vitro Techniques; Lactones; Macrophages; Plants, Toxic; Sesquiterpenes; Sesquiterpenes, Guaiane

Mast cell degranulation was quantitated by measuring percentage of histamine release, 45Ca2+ ion influx, or c-AMP cellular levels after stimulation with various concentrations of the sesquiterpene lactones hymenovin, helenalin, or tenulin. Hymenovin and helenalin, which contain an alpha-methylene-gamma-lactone moiety, produced extensive degranulation. Alkylation of the alpha-methylene-gamma-lactone group of these compounds with the amino acid cysteine before mast cell stimulation drastically reduced the capacity of these lactones to stimulate histamine release. Tenulin, which does not contain an alpha-methylene-gamma-lactone moiety, generally stimulated degranulation approximately equal to that of cysteine-treated hymenovin or helenalin. These data indicate that sesquiterpene lactones containing alpha-methylene-gamma-lactone are potent stimulators of mast cell degranulation. This phenomenon may have a significant role in the toxicity of some sesquiterpene lactones of poisonous plants when ingested by livestock.

Topics: Animals; Antineoplastic Agents, Phytogenic; Ascitic Fluid; Calcium; Cells, Cultured; Chemical Phenomena; Chemistry; Cyclic AMP; Cytoplasmic Granules; Histamine Release; Lactones; Mast Cells; Mutagens; Rats; Rats, Inbred Strains; Sesquiterpenes; Sesquiterpenes, Guaiane; Toxins, Biological

Three sesquiterpene lactones (hymenoxon, helenalin, and tenulin) were tested for genotoxicity using six strains of Bacillus subtilis. Hymenoxon was found to produce lethal DNA damage in strains rec A8 and mc-1 while helenalin was lethal in strains mc-1 and rec E4. Tenulin did not produce lethal DNA damage in any of the strains tested.

Topics: Bacillus subtilis; DNA Repair; DNA, Bacterial; Mutation; Sesquiterpenes; Sesquiterpenes, Guaiane