title: HPLC-based activity profiling--discovery of sanggenons as GABAA receptor modulators in the traditional Chinese drug Sang bai pi (Morus alba root bark).
abstract: EtOAc extracts from two batches of Morus alba root bark (Sang bai pi) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes, which transiently expressed GABA (A) receptors of the subunit composition α₁β₂γ(2S). 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 GABA (A) receptor modulators. The structurally related compound kuwanon L (1) was inactive. The sanggenons represent a new scaffold of positive GABA (A) receptor modulators.
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Igor
authors.initials: I
authors.lastname: Baburin
authors.forename: Janine
authors.initials: J
authors.lastname: Zaugg
authors.forename: Samad Nejad
authors.initials: SN
authors.lastname: Ebrahimi
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002867:Chromones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018757:GABA Modulators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D031625:Morus / Q000737:chemistry*; D009865:Oocytes; D024301:Plant Bark / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D001572:Benzofurans; D002867:Chromones; D004365:Drugs, Chinese Herbal; D018757:GABA Modulators; D011963:Receptors, GABA-A; C579694:sanggenon G; D005680:gamma-Aminobutyric Acid; C477157:sanggenone C