Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation.
Kampo formulations are traditional herbal medications used in China and Japan for many centuries to treat diarrheal diseases such as cholera. Our studies were undertaken to identify and verify by chemical synthesis the active components that inhibited cholera toxin (CT), the virulence factor secreted by Vibrio cholerae, the causative agent of cholera. The Kampo formulation, Daio-kanzo-to, inhibited CT activities (i.e., ADP-ribosylation, Chinese hamster ovary cell elongation); in Daio-kanzo-to, Daio (Rhei rhizoma) was responsible for this effect. Among several components purified from Daio extract, rhubarb galloyl-tannin, a compound characterized by a polygallate structure, was the most effective. To define the active component, gallate analogues similar to rhubarb galloyl-tannin were synthesized. These gallate compounds inhibited all CT activities including ADP-ribosylation, elongation of Chinese hamster ovary cells, and importantly, fluid accumulation in ileal loops. Thus, Kampo formulations or their gallate components might be effective adjunctive therapy with oral rehydration solution for the severe diarrhea of cholera.
Oi
Hiroshi
H
Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Matsuura
Daisuke
D
Miyake
Masami
M
Ueno
Masamiti
M
Takai
Izumi
I
Yamamoto
Takeshi
T
Kubo
Masayoshi
M
Moss
Joel
J
Noda
Masatoshi
M
D000246:Adenosine Diphosphate Ribose; D000818:Animals; D016466:CHO Cells; D002240:Carbohydrate Sequence; D002772:Cholera Toxin / Q000378:metabolism*; D006224:Cricetinae; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005707:Gallic Acid / Q000138:chemical synthesis / Q000494:pharmacology*; D029001:Herbal Medicine; D007082:Ileum; D020835:Medicine, Kampo; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology; D011817:Rabbits; D013634:Tannins / Q000138:chemical synthesis / Q000494:pharmacology*; D014734:Vibrio cholerae
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D013634:Tannins; D000246:Adenosine Diphosphate Ribose; D005707:Gallic Acid; D002772:Cholera Toxin