Isolation and identification from Salvia officinalis of two diterpenes which inhibit t-butylbicyclophosphoro[35S]thionate binding to chloride channel of rat cerebrocortical membranes in vitro.

Ethanolic extracts from dried leaves of sage (Salvia officinalis) showed inhibition of [35S]tertiary-butylbicyclophosphorothionate ([35S]TBPS) binding to rat brain membranes in vitro. This ligand is considered to bind to the chloride channel of the GABA/benzodiazepine receptor complex in brain tissue. Substances having inhibitory activity were purified and their chemical structure identified as the diterpenes carnosic acid and carnosol (IC50 values of 33 +/- 3 microM and 57 +/- 4 microM, respectively). The two compounds did not affect binding of the ligands [3H]muscimol and [3H]diazepam to the GABA/benzodiazepine complex in vitro. Saturation experiments of [35S]TBPS binding indicated that carnosic acid decreases the binding affinity.