Constituents of sage (Salvia officinalis) with in vitro affinity to human brain benzodiazepine receptor

Benzodiazepine receptor binding assay-guided fractionation of the methanol extract from sage leaves (Salvia officinalis L.) revealed three flavones and two abietane diterpenes functioning as benzodiazepine receptor-active components. Structural elucidation of the isolated pure compounds was performed by UV, EIMS, ESIpos-MS/MS, as well as H-1- and C-13-NMR techniques. The flavones apigenin, hispidulin and cirsimaritin competitively inhibited H-3-flumazenil binding to the benzodiazepine receptor with IC50 Values of 30,13 and 350 muM, respectively. In addition, the affinities of the newly discovered diterpene receptor ligands, i.e., 7-methoxyrosmanol and galdosol, were characterized. 7-Methoxyrosmanol exhibited an IC50 value of 7.2 muM and galdosol showed the strongest binding activity to the benzodiazepine receptor with an IC50 value of 0.8 muM.