Antibacterial activity of a novel synthetic progesterone species carrying a linoleic acid molecule against Helicobacter pylori and the hormonal effect of its steroid on a murine macrophage-like cell line

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 140; pp. 17 - 25
• Main Authors: Amgalanbaatar, Avarzed, Shimomura, Hirofumi, Hosoda, Kouichi, Hayashi, Shunji, Yokota, Kenji, Hirai, Yoshikazu
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2014
• Subjects: 17α-Hydroxyprogesterone; 17α-Hydroxyprogesterone caproate; 17α-Hydroxyprogesterone linoleic acid ester; 2,6-di-O-methyl-β-cyclodextrin; Animals; Anti-Bacterial Agents - pharmacology; Bacteriolysis - drug effects; Cell Line; Cell Membrane - drug effects; Cell Membrane - metabolism; Helicobacter pylori; Helicobacter pylori - drug effects; Macrophages - drug effects; Mice; Nitric Oxide - biosynthesis; Phosphatidylethanolamines - metabolism; Progesterone; Progesterone - analogs & derivatives; Progesterone - metabolism; Progesterone - pharmacology; PPLO; 2,6-di-O-methyl-β-cyclodextrin; 17hP4; Preg4; MTT; 17α-Hydroxyprogesterone linoleic acid ester; LPS; CGs; 17hpl; 17α-Hydroxyprogesterone; Helicobacter pylori; PE; PG-CL; 17α-Hydroxyprogesterone caproate; 17hPC; dMβCD; Progesterone; FC; cholesteryl glucosides; pleuropneumonia-like organisms; free cholesterol; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide; 17α-hydroxyprogesterone caproic acid ester; phosphatidylglycerol-cardiolipin; phosphatidylethanolamine; lipopolysaccharide
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2013.10.023

•Progesterone linoleate (PL) binds phosphatidylethanolamine (PE) of H. pylori.•PE is released from H. pylori cell via the interaction with PL.•PL ultimately lyses H. pylori cells.•Bactericidal effect of PL is selective to H. pylori.•PL could be an oral medicine for selectively treating H. pylori-infected patients. Helicobacter pylori, a pathogen responsible for gastric and duodenal diseases, absorbs various steroid compounds into the cell membrane even though some are toxic to this bacterium. An earlier study by our group has demonstrated that progesterone is bactericidal to H. pylori. In this study, we newly synthesized a steroid compound, 17α-hydroxyprogesterone linoleic acid ester (17hPL), to examine antibacterial activity against H. pylori. As expected, 17hPL acted as a bactericidal agent to H. pylori and had no effect on the survival of other common bacterial species. This steroidal substance interacted with phosphatidylethanolamine (PE) on the outer membrane of H. pylori to induce the release of PE from the bacterial cell membrane and to ultimately lyse the bacterial cells. One of the hormonal effects of progesterone is the inhibition of nitric oxide (NO) production from mouse macrophages activated by lipopolysaccharide (LPS). We therefore examined the inhibition effect of 17hPL on the NO production of RAW 264.7 cells, a murine macrophage-like cell line, stimulated with LPS and demonstrated that 17hPL is relatively weaker in its capability to inhibit NO production in LPS-activated cells than progesterone. These results suggest the possibility that 17hPL could be an oral medicine for selectively treating patients infected with H. pylori.