Researchers looking for new drug leads to modulate the GABAA receptor came across aristolactone, a characteristic marker for Aristolochia species, in an imported European sample of Bupleurumchinense roots. Further analysis via HPTLC and macroscopic inspection revealed the sample to be a mixture of both B. chinense and A. manshuriensis roots. Toxic aristolochic acids were confirmed to be present by HPTLC. This issue has long been identified in AHPA's list of Known Adulterants, a section in the association's Guidance Policies.
Discovery of GABAA Receptor Modulator Aristolactone in a Commercial Sample of the Chinese Herbal Drug "Chaihu" (Bupleurum chinense Roots) Unravels Adulteration by Nephrotoxic Aristolochia manshuriensis Roots
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 IGABA 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 (1) 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.