Flavonoids from Perovskia atriplicifolia and Their in Vitro Displacement of the Respective Radioligands for Human Opioid and Cannabinoid Receptors.

Bioassay-guided fractionation of the leaves of Perovskia atriplicifolia (Russian sage) resulted in the isolation of four previously known flavonoid derivatives, 5-hydroxy-6,7,3′,4′-tetramethoxyflavone (1), 5,7-dihydroxy-6,3′,4′-trimethoxyflavone (2), 5-hydroxy-6,7,4′-trimethoxyflavone (3), and 5,7-dihydroxy-6,4′-dimethoxyflavone (4). Compounds 1, 3, and 4 showed displacement of the radioligand for the cloned human δ opioid receptor with Ki values ranging from 3.1 to 26.0 μM. In addition, the binding mode of the compounds in the active site of the δ opioid receptor was investigated through molecular modeling algorithms. This study may have implications in better understanding non-nitrogenous δ opioid receptor ligands.