5,7-Dihydroxy-6-methoxyflavone, a benzodiazepine site ligand isolated from Scutellaria baicalensis Georgi, with selective antagonistic properties.
As part of an effort to identify naturally occurring GABA(A) receptor benzodiazepine binding site (BDS) ligands from traditional medicinal herbs, we previously reported that flavonoid derivatives isolated from Scutellaria baicalensis (S. baicalensis) Georgi exhibited significant affinities for the BDS. The present study describes the characterization of 5,7-dihydroxy-6-methoxyflavone (oroxylin A), one of the major components of the herbal extract. Oroxylin A inhibited [3H]flunitrazepam binding to rat cerebral cortical membrane with a IC(50) value of 1.09+/-0.07 microM. A GABA ratio of 1.09+/-0.04 suggests that oroxylin A interacts as an antagonist at the recognition site. In neuropharmacological studies, oral administration of oroxylin A (3.75-60 mg kg(-1)) did not result in significant changes in animal models routinely employed for benzodiazepine (BD) evaluation. However, oroxylin A selectively abolished the anxiolytic, myorelaxant and motor incoordination, but not the sedative and anticonvulsant effects elicited by diazepam, a BDS agonist. These results add oroxylin A to the list of CNS active flavonoids, and as the first naturally occurring member endowed with selective antagonistic actions via the BDS.
Huen
Michael S Y
MS
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Leung
Justin W C
JW
Ng
Wah
W
Lui
W S
WS
Chan
Michelle N S
MN
Wong
J Tze-Fei
JT
Xue
Hong
H
D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D004365:Drugs, Chinese Herbal; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008024:Ligands; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010852:Picrotoxin; D010946:Plants, Medicinal / Q000737:chemistry; D011597:Psychomotor Performance / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis / Q000737:chemistry*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D008024:Ligands; D010852:Picrotoxin; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one