2. Academic Validation
  3. Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing

Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing

  • Life Sci. 2020 May 1;248:117456. doi: 10.1016/j.lfs.2020.117456.
Tao Yang 1,  Ruilin Wang 2,  Jianzhong Zhang 3,  Chunmei Bao 4,  Juling Zhang 4,  Ruisheng Li 5,  Xing Chen 6,  Shihua Wu 6,  Jianxia Wen 6,  Shizhang Wei 7,  Haotian Li 7,  Huadan Cai 7,  Xiangdong Yang 8,  Yanling Zhao 9
Affiliations

Affiliations

  • 1 College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, No. 37, 12 Bridge Road, Chengdu 610075, PR China.
  • 2 Integrative Medical Center, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China.
  • 3 Center of Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing 100039, PR China.
  • 4 Division of Clinical Microbiology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China.
  • 5 Research Center for Clinical and Translational Medicine, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China.
  • 6 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
  • 7 Department of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China.
  • 8 Colorectal and Anal Surgery, Chengdu Anorectal Hospital, No 152 Daqiang East Street, Taisheng South Road, Chengdu 610075, PR China. Electronic address: y-xd@vip.163.com.
  • 9 Department of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China. Electronic address: zhaoyl2855@126.com.
PMID: 32097666 DOI: 10.1016/j.lfs.2020.117456
Abstract

Aims: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated.

Materials and methods: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured.

Key findings: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

Keywords

Berberine; Chronic atrophic gastritis; Helicobacter pylori; IFN-γ; IRF8.

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