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
  • 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: [email protected].
  • 9. Department of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China. Electronic address: [email protected].
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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