title: (-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.
abstract: (-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions.
authors.affiliation: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China; School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Xie
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Zhixiu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Xian
authors.affiliation: College of Science, Guangdong Ocean University, Zhanjiang, Guangdong, PR China; School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Songzhi
authors.initials: S
authors.lastname: Kong
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Lai
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
authors.forename: Siupo
authors.initials: S
authors.lastname: Ip
authors.affiliation: The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Guo
authors.affiliation: The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Zuqing
authors.initials: Z
authors.lastname: Su
authors.affiliation: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address: yy92009@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, ,PR China. Electronic address: suziren@gzucm.edu.cn.
authors.forename: Ziren
authors.initials: Z
authors.lastname: Su
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism; D002384:Catalysis / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D018384:Oxidative Stress / Q000187:drug effects; D000070177:Pogostemon / Q000276:immunology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014510:Urease / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D012717:Sesquiterpenes; D014510:Urease; C052983:patchouli alcohol
keywords: Apoptosis; Helicobacter pylori urease; Human gastric epithelial cells; Inflammatory; Oxidative; Patchouli alcohol