Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter, is metabolized by the successive action of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Inhibition of both enzymes in brain tissues increases the GABA level and may have therapeutic applications in neurological diseases. Erigeron breviscapus ethanol extract was evaluated for their effect on both enzymes. This extract, its ethyl acetate fraction and aqueous fraction, significantly inhibited them at >100 microg/ml. Flavonoid components of E. breviscapus potently and noncompetitively inhibited both enzymes, and the different structure-activity relations were observed with respect to inhibition of both enzymes. Baicalein was the most potent inhibitor for GABA-T with an IC50 value of 12.8+/-1.2 microM, and scutellarein exhibited the best inhibitory effect on SSADH with an IC50 value of 7.20+/-0.9 microM. The present results may imply new pharmacological actions of E. breviscapus and contribute partially to the beneficial effect of the herb and flavonoids on the central nervous system.