

Nathan Seppa
For centuries, Chinese and Japanese healers have used traditional medicines to combat the overwhelming diarrhea that comes with cholera. Researchers in Japan have identified a natural compound responsible for the effectiveness of one rhubarb-based remedy, a finding that could lead to even better pharmaceutical therapies.
The scientists tested a formulation called Daio-Kanzo-to. One chemical in the mixture, rhubarb galloyl-tannin, inhibits cholera toxin's effects on hamster cells in a test tube, the researchers found. The rhubarb compound binds to the toxin and apparently disables it, the researchers report in the March 5 issue of the Proceedings of the National Academy of Sciences.
The team also tested rhubarb galloyl-tannin and other chemical constituents of the traditional remedy by injecting them one by one into the intestines of mice and rabbits exposed to cholera toxin. Rhubarb galloyl-tannin reduced fluid accumulation in the intestines—a sign of severe diarrhea—10 times better than the next-best ingredient did, says study coauthor Masatoshi Noda, a molecular microbiologist of the Chiba University Graduate School of Medicine in Japan.
"This is a beautiful example of taking this sort of traditional information and chasing it down to the pharmaceutical level," says John J. Mekalanos, a microbiologist at Harvard Medical School in Boston.
The current standard of care for people with cholera is oral-rehydration therapy—plenty of fluids mixed with some essential salts. Drugs can also help by killing Vibrio cholera, the bacterium that makes the toxin.
Although rhubarb galloyl-tannin worked best in this study when given before the animals were exposed to cholera toxin, Noda says he thinks it could help people with cholera as part of a "triple therapy," with antibiotics and oral rehydration. Still unclear, says Mekalanos, is how well rhubarb galloyl-tannin would penetrate the mucous membrane that lines intestines and get at cholera toxin in an infected person.
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Oi, H., … and M. Noda. 2002. Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation. Proceedings of the National Academy of Sciences 99(March 5):3042–3046. Abstract available at http://dx.doi.org/10.1073/pnas.052709499.
Badizadegan, K., et al. 2000. Floating cholera toxin into epithelial cells: Functional association with caveolae-like detergent-insoluble membrane microdomains. International Journal of Medical Microbiology 290:403–408.
John J. Mekalanos
Harvard Medical School
200 Longwood Avenue
Boston, MA 02115
Masatoshi Noda
Department of Molecular Infectiology
Graduate School of Medicine
Chiba University
1-8-1 Inohana, Chuo-ku
Chiba 260-8670
Japan
From Science News, Volume 161, No. 13, March 30, 2002, p. 205.