idney function
problems occurred frequently in Belgium in 1993 as the result of an herbal
medicine produced in China that was used to treat obesity. The cause of
this syndrome, which is referred to as "Chinese herb nephropathy,"
is believed to be aristolochic acid, one of the compounds that occurs in
a plant in the Aristolochia clematis family that is used in Chinese herbal
medicine. In 1995, the same type of problem was encountered in Japan when instances of Fanconi syndrome occurred among adults and were studied by Prof. Ritsuo Nishida and his colleagues at Kyoto University. Since aristolochic acid was detected in the Chinese herbal medicine which had been taken by the patients, it was thought that their ailment was similar to the Chinese herb nephropathy seen in Belgium. Investigation confirmed that there had been 10 cases reported in Japan since 1993, and that all patients were suspected of having taken Chinese herbal medicine containing an herb derived from the Aristolochia clematis family. A cautionary warning was published in the journal of the Japanese Society of Nephrology.
The renal toxicity of the aristolochic acid contained in this family of plants has been established experimentally. Aristolochic acid administered to rats caused dose-dependent kidney damage within three days. Damage included destruction of the epithelium of the ureter, an increase of sugar, protein and NAG (N-acetyl-Beta-D-Glucosaminidase) in the urine, and an elevation of BUN and creatinine in the blood. While the symptoms reported in this research differed as to degree, kidney damage found in animal studies was similar to that incurred by the patients suffering from Chinese herb nephropathy in Belgium. Therefore, aristolochic acid was believed to be the cause of renal morbidity reported in Japan.
| @ |  |
| @ | Aristolochia manshuriensis
Kom, a member of the Aristolochia clematis family not included in
the basic Kampo compendia causes serious kidney problems. |
It became clear that of the 10 cases in Japan, five had taken herbal medicine produced in China and sold by a firm in Osaka. Sales were then halted and a product recall of the suspect product was carried out in July of 1997. The imported Chinese herbal medicine contained the root and stem of an Aristolochia clematis family plant called Aristolochia manshuriensis Kom, which is not contained in the basic compendia used by Kampo manufacturers in Japan, the Japanese Pharmacopeia (JP) and the Japanese Herbal Medicine Codex (JHMC).
Aristolochia manshuriensis Kom, called Kan-Mokutsu in Japanese, is completely unrelated to Mokutsu (Akebia quinta Decaisne), which is included in the JP and for which, in this case, it had been substituted. Mokutsu, which is included in the JP and used in Japanese Kampo medicines is the stem of the Akebia quinta Decaisne and is not considered to be toxic. Unlike Kan-Mokutsu, it does not contain aristolochic acid. In contrast, Kan-Mokutsu does contain aristolochic acid and, as explained above, is not included in the JP. It should be added that the Drug Regulation Department of the German Federal Republic prohibits the sale of drugs containing aristolochic acid.
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| Toxic herb in imported formulation
was mistaken for Akebia quinta Decaisne (above), a non-toxic herb
used in Kampo medicines. |
The approval and standardization of herbal medicines differ from country to country, as does the enforcement of herbal medicine regulation. Thus, in order to ensure the safety of herbal medicines, it is very important to verify the origin of the plant matter being used and then to carry out product quality assurance during the manufacturing process. The incident just cited indicates the particular importance of these quality assurance procedures in protecting the users of herbal medicines.