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An EtOAc extract from the roots of Sophora flavescens (Kushen) potentiated gamma-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes transiently expressing GABA(A) receptors with subunit composition, alpha (1) beta (2) gamma (2S). HPLC-based activity profiling of the extract led to the identification of 8-lavandulyl flavonoids, kushenol I, sophoraflavanone G, (-)-kurarinone, and kuraridine as GABA(A) receptor modulators. In addition, a series of inactive structurally related flavonoids were characterized. Among these, kushenol Y (4) was identified as a new natural product. The 8-lavandulyl flavonoids are first representatives of a novel scaffold for the target.