RAPID IN VIVO SCREENING METHOD FOR THE EVALUATION OF NEW ANTI HELICOBACTER MEDICINAL PREPARATIONS

Abstract

The objective of this study was to devise a rapid mouse model for the in vivo screening of new anti Helicobacter pylori products. Six to eight week-old mice pre-treated (7 days) with Amoxicillin/Metronidazole (25 mg/kg) to eliminate all Helicobacter-like organisms were inoculated (4x per week) with 200 µl of a bacterial culture (108 CFU/ml of H. pylori CCUG-39500). Colonisation of mouse stomach was assessed from day 1 to 15 post inoculation by the Gram stain, rapid urease test and antral mucus culture. These findings were used as a mouse model of Helicobacter pylori infection to assess the in vivo anti Helicobacter activities of two plant-derived molecules with proven cytoprotective, ulcer healing and in vitro anti Helicobacter properties (TN, a tabersonine chloride alkaloid from the fruits of Voacanga Africana and PAL, a protoberberine alkaloid ((7,8-dihydro-8-hydroxy-palmatine) from the bark of Enantia chlorantha). For up to 6 days post inoculation, the test organisms were recoverable by culture from 87.5% of the antral mucus samples while 100% of Gram stains were positive. The infection tended to clear naturally from day 9. Fifteen days post infection, only Gram stains were still positive (37.5%). Three-day oral administration of TN, PAL (50 mg/kg) and Metronidazole (25 mg/kg) completely eliminated the bacterial strain from the gastric antral mucus compared with the controls. This 4-week model is proposed as a rapid screening tool for in vivo evaluation of new anti H. pylori products in order to select candidates for detailed investigations.