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bioRxiv · 10.1101/846790

Inhibitory effects of β-caryophyllene on Helicobacter pylori infection in vitro and in vivo

Woo, H. J.·Yang, J. Y.·Lee, M. H.·Kim, H. W.·Kwon, H. J.·Park, M.·Kim, S.-k.·Park, S.-Y.·Kim, S.-H.·Kim, J.-B.
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Abstract

The human specific bacterial pathogen Helicobacter pylori (H. pylori) is a Gram-negative microaerophilic bacterium and associated with severe gastric diseases such as peptic ulceration and gastric cancer. Recently, the increasing resistance and the emergence of adverse effects make the usage of antibiotics less effectively. Therefore, development of new antimicrobial agent is required to control H. pylori infection. In the current study, it has been demonstrated the inhibitory effect of {beta}-caryophyllene on H. pylori growth and the protective effect against H. pylori infection as well as antibacterial therapeutic effect. {beta}-caryophyllene inhibited H. pylori growth via down-regulation of dnaE, dnaN, holB and gyrA and also down-regulated virulence factors such as CagA, VacA and SecA proteins. {beta}-caryophyllene inhibited expression of several type IV secretion system (T4SS) components including virB2, virB4 and virB8, so that CagA translocation into H. pylori-infected AGS cells was decreased by {beta}-caryophyllene treatment. {beta}-caryophyllene also inhibited VacA toxin entry through down-regulation of type IV secretion system (T5SS). In vivo experiments using Mongolian gerbils demonstrated antibacterial therapeutic effects of {beta}-caryophyllene. After {beta}-caryophyllene administration, immunohistochemistry (IHC) stain using anti-H. pylori antibody showed the antibacterial effect and H&E stain showed the therapeutic effect in treated groups. Hematological data which conformed with histological data support the therapeutic effect of {beta}-caryophyllene administration. Such a positive effect of {beta}-caryophyllene on H. pylori infection potently substantiate that this natural compound could be used as a new antimicrobial agent or functional health food to help the patients whom suffering from gastroduodenal diseases due to H. pylori infection. Author summaryThe inhibitory effect on {beta}-caryophyllene on H. pylori growth and the protective effect against H. pylori infection as well as antibacterial therapeutic effect have been elucidated in this study. {beta}-caryophyllene inhibited H. pylori growth via downregulation of replication machinery of H. pylori. {beta}-caryophyllene also downregulated virulence factors such as CagA, VacA and SecA proteins which are necessary for successful colonization and pathogenesis of H. pylori. Besides, {beta}-caryophyllene significantly reduced H. pylori-induced actin-cytoskeletal rearrangement, vacuolation and apoptosis in AGS cells. In in vivo infection model, {beta}-caryophyllene showed splendid therapeutic effect against H. pylori infection. In particular, this is the first report that evaluates the toxicological effects of {beta}-caryophyllene administration on Mongolian gerbils. Such a positive effect of {beta}-caryophyllene on H. pylori infection potently substantiate that this natural compound could be used as a new antimicrobial agent or functional health food to help the patients whom suffering from gastroduodenal diseases due to H. pylori infection.

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Woo, H. J., Yang, J. Y., Lee, M. H., Kim, H. W., Kwon, H. J., Park, M., Kim, S.-k., Park, S.-Y., Kim, S.-H., Kim, J.-B.. 2019-11-18. Inhibitory effects of β-caryophyllene on Helicobacter pylori infection in vitro and in vivo. https://doi.org/10.1101/846790

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