EtOAc extracts from two batches of Morus alba root bark (Sang bai pi) potentiated -aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes, which transiently expressed GABAreceptors of the subunit composition 2 With the aid of HPLC-based activity profiling of the extract from the first batch, activity was traced to a peak subsequently identified as sanggenon G (3). The second batch had a different phytochemical profile, and HPLC-based activity profiling led to the identification of sanggenon C (4) and a stereoisomer of sanggenon D (2) as positive GABAreceptor modulators. The structurally related compound kuwanon L (1) was inactive. The sanggenons represent a new scaffold of positive GABAreceptor modulators.