Inhibitory Effects of β-Caryophyllene on Helicobacter pylori Infection In Vitro and In Vivo

Abstract

The human specific bacterial pathogen <i>Helicobacter pylori</i> (<i>H. pylori</i>) is associated with severe gastric diseases, including gastric cancer. Recently, the increasing resistance makes the usage of antibiotics less effectively. Therefore, development of a new antimicrobial agent is required to control <i>H. pylori</i> infection. In the current study, the inhibitory effect of β-caryophyllene on <i>H. pylori</i> growth, as well as the antibacterial therapeutic effect, has been demonstrated. β-caryophyllene inhibited <i>H. pylori</i> growth via the downregulation of <i>dna</i>E, <i>dna</i>N, <i>hol</i>B, and <i>gyr</i>A and also downregulated virulence factors such as CagA, VacA, and SecA proteins. β-caryophyllene inhibited expression of several T4SS components, so that CagA translocation into <i>H. pylori</i>-infected AGS gastric cancer cells was decreased by β-caryophyllene treatment. β-caryophyllene also inhibited VacA entry through the downregulation of T5_aSS. After β-caryophyllene administration on Mongolian gerbils, the immunohistochemistry (IHC) and Hematoxylin&Eosin stains showed therapeutic effects in the treated groups. Hematological data, which was consistent with histological data, support the therapeutic effect of β-caryophyllene administration. Such a positive effect of β-caryophyllene on <i>H. pylori</i> infection potently substantiates the natural compound as being capable of being used as a new antimicrobial agent or functional health food to help patients who are suffering from gastroduodenal diseases due to <i>H. pylori</i> infection.