Ginger (Zingiber Officinale Roscoe, Zingiberaceae) Extract And 10- Gingerol Enhance The Activity Of Clarithromycin Against Resistant Helicobacter Strains

Abstract

Previously, we have demonstrated that a methanol extract of ginger rhizome inhibited the growth of Helicobacter pylori (HP) in vitro (MIC range of 0.78 to 12.5 µg/ml), with the gingerols being the active constituents [1] Furthermore, the ginger extract reduced HP load in Mongolian gerbils and significantly reduced both acute and chronic muscosal and submucosal inflammation, cryptitis, as well as epithelial cell degeneration and erosion induced by HP [2]. Since clarithromycin is a key component of many therapeutic regimens recommended for H. pylori eradication, and that resistance to clarithromycin has emerged, we tested the ginger extracts and gingerols for possible synergism with clarithromycin in 12 HP clinical isolates. The combination effect of antibiotics and ginger extract/gingerols in agar medium was determined using the checkerboard assay and evaluated using the fractional inhibitory concentration (FIC) index. The combination of clarithromycin and the ginger extract or 10-gingerol was synergistic in 8 of the clinical HP strains tested, including the 5 clarithromycin resistant strains, as well as the ATCC 43504 control strain. The results from the FIC checkerboard showed that more than 80% of all clinical isolates, were susceptible to the effect of the combination of ginger extract/or 10-gingerol and clarithromycin, with synergistic and additive effects. For clinical isolate #10, the MIC of clarithromycin (CL) decreased significantly from 100 µg/ml to 6.25 µg/ml, in the presence of 10 µg/ml 10-gingerol. These data support the hypothesis that specific natural products have additive and synergistic effects with clarithromycin against CL-susceptibile and CL-resistant HP strains.