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 (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.

Bupleurum chinense - Apiaceae - Aristolochia sp. - Aristolochiaceae - aristolactone - aristolochic acids - traditional Chinese medicine - adulteration

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