title: Discovery of GABA(A) receptor modulator aristolactone in a commercial sample of the Chinese herbal drug "Chaihu" (Bupleurum chinense roots) unravels adulteration by nephrotoxic Aristolochia manshuriensis roots.
abstract: In a two-microelectrode voltage clamp assay using Xenopus laevis oocytes, a petroleum ether extract prepared from a commercial sample of the traditional Chinese herbal drug labelled as " Chaihu" (Bupleurum chinense DC. roots) enhanced the I(GABA) by 156 % ± 22 % when tested at 100 µg/mL. By means of HPLC-based activity profiling combined with high-resolution LC-MS and microprobe NMR, the germacranolide aristolactone was identified as one of the main active compounds (EC₅₀ 56.02 µM ± 5.09 µM). However, aristolactone has been previously reported only from the genus Aristolochia (Aristolochiaceae), suggesting a possible adulteration. With the aid of a validated HPTLC protocol for detection of aristolochic acids and with reference samples, the commercial sample was confirmed to be a mixture of Aristolochia manshuriensis root and Bupleurum chinense root. This finding was corroborated by macroscopic inspection of the drug. This case of adulteration with a highly nephrotoxic drug raises concerns about adequate quality control of TCM drugs commercialized in Europe.
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rueda
authors.forename: Janine
authors.initials: J
authors.lastname: Zaugg
authors.forename: Melanie
authors.initials: M
authors.lastname: Quitschau
authors.forename: Eike
authors.initials: E
authors.lastname: Reich
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D000818:Animals; D030022:Aristolochia / Q000737:chemistry* / Q000633:toxicity*; D034341:Aristolochic Acids / Q000737:chemistry* / Q000633:toxicity*; D029972:Bupleurum / Q000737:chemistry*; D004340:Drug Contamination; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D009865:Oocytes / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011963:Receptors, GABA-A / Q000378:metabolism; D018675:Toxicity Tests; D014981:Xenopus
chemical_list: D034341:Aristolochic Acids; C051274:Bupleurum root extract; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011963:Receptors, GABA-A