Lubeluzole: from anti-ischemic drug to preclinical antidiarrheal studies.

BACKGROUND: Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea. METHODS: In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility. RESULTS: Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. CONCLUSION: All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity.

Chronic treatment with epigallocatechin gallate reduces motor hyperactivity and affects in vitro tested intestinal motility of spontaneously hypertensive rats.

BACKGROUND: Green tea catechins seem to contribute toward reducing body weight and fat. OBJECTIVE: We aimed to investigate whether chronic administration of (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. DESIGN: Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 µM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. RESULTS: Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle-treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05-5 µM) and increased inhibitory response to electrical field stimulation (EFS, 1-10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG incubation (100 µM, 20 min) of colonic and duodenum strips obtained from untreated SHR and WKY rats showed a reduced contractile colonic response to a fixed dose of carbachol (1.5 µM) only in SHR with respect to its own vehicle, whereas the inhibitory duodenal response to a fixed EFS frequency (5 Hz) was significantly reduced in both WKY rats and SHR groups with respect to their own vehicle. CONCLUSIONS: These data suggest that EGCG affects body weight gain in rats and this effect seems to be due to the altered intestinal motility and not to increased motor activity.