title: Bioactivity-guided isolation of GABA(A) receptor modulating constituents from the rhizomes of Actaea racemosa.
abstract: Black cohosh (Actaea racemosa) is a frequently used herbal remedy for the treatment of mild climacteric symptoms. In the present study, the modulation of γ-aminobutryic acid (GABA)-induced chloride currents (I(GABA)) through GABA type A (GABA(A)) receptors by black cohosh extracts and isolated compounds was investigated. GABA(A) receptors, consisting of α(1), β(2), and γ(2S) subunits, were expressed in Xenopus laevis oocytes, and potentiation of I(GABA) was measured using the two-microelectrode voltage clamp technique. In a bioactivity-guided isolation procedure the positive modulation of I(GABA) could be restricted to the plant terpenoid fractions, resulting in the isolation of 11 cycloartane glycosides, of which four significantly (p < 0.05) enhanced I(GABA). The most efficient effect was observed for 23-O-acetylshengmanol 3-O-β-d-xylopyranoside (4, 100 μM), enhancing I(GABA) by 1692 ± 201%, while actein (1), cimigenol 3-O-β-d-xylopyranoside (6), and 25-O-acetylcimigenol 3-O-α-l-arabinopyranoside (8) were significantly less active. In the absence of GABA, only 4 induced small (not exceeding 1% of I(GABA-max)) chloride inward currents through GABA(A) receptors. It is hypothesized that the established positive allosteric modulation of GABA(A) receptors may contribute to beneficial effects of black cohosh extracts in the treatment of climacteric symptoms.
authors.affiliation: Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 52c, Innsbruck, Austria.
authors.forename: Serhat S
authors.initials: SS
authors.lastname: Cicek
authors.forename: Sophia
authors.initials: S
authors.lastname: Khom
authors.forename: Barbara
authors.initials: B
authors.lastname: Taferner
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
mesh_terms: D000818:Animals; D001317:Austria; D031885:Cimicifuga / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects*; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: C478830:(23R,24S)-16,23-16,24-diepoxy-9,19-cyclolanostan-3beta,15alpha,25-triol; D006027:Glycosides; D010936:Plant Extracts; D011963:Receptors, GABA-A; D012503:Saponins; D014315:Triterpenes; D007810:Lanosterol; C096064:actein