Article Publish Status: FREE
Abstract Title:

Inhibition by apple polyphenols of ADP-ribosyltransferase activity of cholera toxin and toxin-induced fluid accumulation in mice.

Abstract Source:

Microbiol Immunol. 2002 ;46(4):249-55. PMID: 12061627

Abstract Author(s):

Takao Saito, Masami Miyake, Masamichi Toba, Hiroshi Okamatsu, Seiichi Shimizu, Masatoshi Noda

Article Affiliation:

Takao Saito

Abstract:

The effects of crude polyphenol extracted from immature apples on the enzymatic and biological activities of a cholera toxin (CT) were investigated. When the apple polyphenol extract (APE) was examined for properties to inhibit CT-catalyzed ADP-ribosylation of agmatine, it was found that APE inhibited it in a dose-dependent manner. The concentration of APE to inhibit 50% of the enzymatic activity of CT (15 microg/ml) was approximately 8.7 microg/ml. The APE also diminished CT-induced fluid accumulation in two diarrhea models for in vivo mice. In the ligated ileum loops, 25 microg of APE significantly inhibited fluid accumulation induced by 500 ng of CT. In a sealed mouse model, even when APE was administered orally 10 min after a toxin injection, fluid accumulation was significantly inhibited at a comparable dosage. Lineweaver-Burk analysis demonstrated that APE had negative allosteric effects on CT-catalyzed NAD: agmatine ADP-ribosyltransferase. We fractionated the APE into four fractions using LH-20 Sephadex resin. One of the fractions, FAP (fraction from apple polyphenol) 1, which contains non-catechin polyphenols, did not significantly inhibit the CT-catalyzed ADP-ribosylation of agmatine. FAP2, which contains compounds with monomeric, dimeric, and trimeric catechins, inhibited the ADP-ribosylation only partially, but significantly. FAP3 and FAP4, which consist of highly polymerized catechin compounds, strongly inhibited the ADP-ribosylation, indicating that the polymerized structure of catechin is responsible for the inhibitory effect that resides in APE. The results suggest that polymerized catechin compounds in APE inhibit the biological and enzymatic activities of CT and can be used in a precautionary and therapeutic manner in the treatment of cholera patients.

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