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Toxicology ; 131(2-3): 133-43, 1998 Nov 16.
Article in English | MEDLINE | ID: mdl-9928628

ABSTRACT

Bioactivity-guided fractionation of an alcohol extract of the soft coral Sarcophyton glaucum collected from the intertidal areas and the fringing coral reefs near Hurghada, Red Sea, Egypt resulted in the isolation of a new lactone cembrane diterpene, sarcophytolide. The structure of this compound was deduced from its spectroscopic data and by comparison of the spectral data with those of known closely related cembrane-type compounds. In antimicrobial assays, the isolated compound exhibited a good activity towards Staphylococcus aureus, Pseudomonas aeruginosa, and Saccharomyces cerevisiae. Sarcophytolide was found to display a strong cytoprotective effect against glutamate-induced neurotoxicity in primary cortical cells from rat embryos. Preincubation of the neurons with 1 or 10 microg/ml of sarcophytolide resulted in a significant increase of the percentage of viable cells from 33 +/- 4% (treatment of the cells with glutamate only) to 44 +/- 4 and 92 +/- 6%, respectively. Administration of sarcophytolide during the post-incubation period following glutamate treatment did not prevent neuronal cell death. Pretreatment of the cells with sarcophytolide for 30 min significantly suppressed the glutamate-caused increase in the intracellular Ca2+ level ([Ca2+]i). Evidence is presented that the neuroprotective effect of sarcophytolide against glutamate may be partially due to an increased expression of the proto-oncogene bcl-2. The coral secondary metabolite, sarcophytolide, might be of interest as a potential drug for treatment of neurodegenerative disorders.


Subject(s)
Cnidaria/chemistry , Diterpenes/pharmacology , Neuroprotective Agents/pharmacology , Animals , Calcium/metabolism , Mice , Neuroprotective Agents/isolation & purification , Proto-Oncogene Proteins c-bcl-2/analysis , Rats , Rats, Wistar , Staphylococcus aureus/drug effects
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