Inhibitory effects of β-caryophyllene onHelicobacter pyloriinfectionin vitroandin vivo
Authors: Woo Hyun Jun , Yang Ji Yeong , Lee Min Ho , Kim Hyun Woo , Kwon Hye Jin , Park Min , Kim Sung-kyu , Park So-Young , Kim Sa-Hyun , Kim Jong-Bae 
Published: November 2019

ABSTRACTThe human specific bacterial pathogenHelicobacter 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 controlH. pyloriinfection. In the current study, it has been demonstrated the inhibitory effect of β-caryophyllene onH. pylorigrowth and the protective effect againstH. pyloriinfection as well as antibacterial therapeutic effect. β-caryophyllene inhibitedH. pylorigrowth via down-regulation ofdnaE,dnaN,holB andgyrA and also down-regulated virulence factors such as CagA, VacA and SecA proteins. β-caryophyllene inhibited expression of several type IV secretion system (T4SS) components includingvirB2,virB4 andvirB8, so that CagA translocation intoH. pylori-infected AGS cells was decreased by β-caryophyllene treatment. β-caryophyllene also inhibited VacA toxin entry through down-regulation of type IV secretion system (T5SS).In vivoexperiments using Mongolian gerbils demonstrated antibacterial therapeutic effects of β-caryophyllene. After β-caryophyllene administration, immunohistochemistry (IHC) stain using anti-H. pyloriantibody 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 β-caryophyllene administration. Such a positive effect of β-caryophyllene onH. pyloriinfection 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 toH. pyloriinfection.Author summaryThe inhibitory effect on β-caryophyllene onH. pylorigrowth and the protective effect againstH. pyloriinfection as well as antibacterial therapeutic effect have been elucidated in this study. β-caryophyllene inhibitedH. pylorigrowth via downregulation of replication machinery ofH. pylori. β-caryophyllene also downregulated virulence factors such as CagA, VacA and SecA proteins which are necessary for successful colonization and pathogenesis ofH. pylori. Besides, β-caryophyllene significantly reducedH. pylori-induced actin-cytoskeletal rearrangement, vacuolation and apoptosis in AGS cells. Inin vivoinfection model, β-caryophyllene showed splendid therapeutic effect againstH. pyloriinfection. In particular, this is the first report that evaluates the toxicological effects of β-caryophyllene administration on Mongolian gerbils. Such a positive effect of β-caryophyllene onH. pyloriinfection 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 toH. pyloriinfection.