BACTERICIDAL EFFECT OF PLAUNOTOL, A CYTOPROTECTIVE ANTIULCER AGENT, AGAINST HELICOBACTER-PYLORI

In order to investigate the bactericidal effect of plaunotol, an oily antiulcer agent, against Helicobacter pylori, comparative studies were conducted using its derivatives, M-4, M-5, and M-6, whose hydrophobic ity decreased in the order of plaunotol > M-6 > M-5 > M-4 by log P det ermination. Plaunotol rapidly reduced the viability of H. pylori in vi tro, and cell death was associated with cell lysis. In addition, plaun otol showed eightfold stronger bactericidal activity against H. pylori than M-6 and M-5, while the compound with the lowest hydrophobicity, M-4, showed no bactericidal activity. The bactericidal activities of p launotol and its derivatives were related to the hydrophobicity of the se compounds. To investigate a possible interaction between these comp ounds and the cell membrane of H. pylori, their effects on liposomal m embranes prepared from phosphatidylethanolamine and cardiolipin, which are known to be present in the membrane of H. pylori, were determined by detection of glucose release from the liposomes. Plaunotol showed eight-fold higher activity than M-6 and M-5, while M-4 showed no activ ity. The effects of plaunotol and its derivatives on liposomal membran e were therefore related to their bactericidal activities. In addition , it was confirmed that the bactericidal effect of plaunotol against H . pylori was neutralized by the liposomal membrane, and that plaunotol led to an increase in permeability of the membrane, as evidenced by m easurement of the leakage of 260 nm absorbing-material from H. pylori. These results suggest that the bactericidal effect of plaunotol again st H. pylori is due to the interaction between this compound and the b acterial cell membrane.