In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection

Antimicrob Agents Chemother. 2017 May 24;61(6):e00122-17. doi: 10.1128/AAC.00122-17. Print 2017 Jun.

Abstract

This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 μg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 μg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1β, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.

Keywords: Helicobacter pylori; antiadhesion; antigastritis; antimotility; patchouli alcohol.

MeSH terms

  • Adhesins, Bacterial / biosynthesis
  • Adhesins, Bacterial / genetics
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Adhesion / drug effects
  • Bacterial Outer Membrane Proteins / biosynthesis
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Clarithromycin / pharmacology
  • Female
  • Flagellin / biosynthesis
  • Flagellin / genetics
  • Gastritis / drug therapy*
  • Gastritis / microbiology
  • Gene Expression / drug effects
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / isolation & purification
  • Humans
  • Hydro-Lyases / biosynthesis
  • Hydro-Lyases / genetics
  • Inflammation / drug therapy
  • Inflammation / microbiology
  • Male
  • Metronidazole / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Oxidoreductases / biosynthesis
  • Oxidoreductases / genetics
  • Sesquiterpenes / pharmacology*

Substances

  • Adhesins, Bacterial
  • AlpA protein, Helicobacter pylori
  • AlpB protein, Helicobacter pylori
  • Anti-Bacterial Agents
  • BabA protein, Helicobacter pylori
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • FlaA1 protein, Helicobacter pylori
  • Sesquiterpenes
  • Flagellin
  • flaB flagellin
  • Metronidazole
  • Oxidoreductases
  • Hydro-Lyases
  • Clarithromycin
  • patchouli alcohol