Discovery of GABAreceptor modulator aristolactone in a commercial sample of the chinese herbal drug chaihu (bupleurum chinense roots) unravels adulteration by nephrotoxic aristolochia manshuriensis roots

摘要

In a twomicroelectrode 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 Iby 156% ±22% when tested at 100μg/mL. By means of HPLC-based activity profiling combined with high-resolution LC-MS and microprobe NMR, the germacranolide aristolactone (1) was identified as one of the main active compounds (EC56.02μM±5.09μM). 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.