title: Inhibitory effect of withaferin A on Helicobacter pylori‑induced IL‑8 production and NF‑κB activation in gastric epithelial cells.
abstract: Withaferin A (WA), a withanolide purified from Withania somnifera, has been known to exert anti-inflammatory effects. The present study sought to determine the effects of WA on Helicobacter (H.) pylori-mediated inflammation in the AGS gastric epithelial cell line. Cellular production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) was measured by ELISA. Western blot analysis was performed to determine the activation of nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) as well as hypoxia-inducible factor 1α stabilization. Bacterial growth was also examined by measuring the optical density. Pre-treatment or co-treatment with WA efficiently reduced IL-8 production by AGS cells in response to H. pylori infection. H. pylori-induced activation of NF-κB, but not MAPKs, was also inhibited by pre-treatment of WA in the cells. However, WA did not affect VEGF production and HIF-1α stabilization induced by H. pylori in AGS cells. In addition, WA did not influence the growth of H. pylori, suggesting that the anti-inflammatory effect of WA was not due to any bactericidal effect. These findings indicate that WA is a potential preventive or therapeutic agent for H. pylori-mediated gastric inflammation.
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Green
authors.initials: G
authors.lastname: Kim
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul University, Seoul 151‑742, Republic of Korea.
authors.forename: Tae-Hyoun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Da-Young
authors.initials: DY
authors.lastname: Pack
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Ik-Rae
authors.initials: IR
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Min-Gyu
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Graduate School of Pre‑Clinical Laboratory Science, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Sang-Seop
authors.initials: SS
authors.lastname: Han
authors.affiliation: World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Cheongwon‑Gun, Choongbuk 363‑883, Republic of Korea.
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Sang-Muk
authors.initials: SM
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302‑718, Republic of Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Cheongwon‑Gun, Choongbuk 363‑883, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D054358:Withanolides / Q000008:administration & dosage*
chemical_list: C508606:CXCL8 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D016328:NF-kappa B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D054358:Withanolides; D020928:Mitogen-Activated Protein Kinases; C009684:withaferin A