Zerumbone Suppresses Enterotoxigenic Bacteroides fragilis Infection-Induced Colonic Inflammation through Inhibition of NF-κΒ

• Published in: International journal of molecular sciences Vol. 20; no. 18; p. 4560
• Main Authors: Hwang, Soonjae, Jo, Minjeong, Hong, Ju Eun, Park, Chan Oh, Lee, Chang Gun, Yun, Miyong, Rhee, Ki-Jong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-09-2019; MDPI
• Subjects: Adherens junctions; Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antioxidants; Bacterial infections; Bacterial Toxins; Bacteroides fragilis - metabolism; Bacteroides Infections - drug therapy; Bacteroides Infections - immunology; BFT; Biofilms; Cadherins - metabolism; Carcinogens; Colitis; Colitis - drug therapy; Colitis - immunology; Colon; Colon - drug effects; Colon - immunology; Colon - physiopathology; Colorectal cancer; Cytokines; Disease; Disruption; E-cadherin; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - pathology; Epithelium; ETBF; Helper cells; Herbal medicine; HT29 Cells; Humans; Infections; Inflammation; Inflammatory bowel disease; Interleukin 8; Interleukin-17 - metabolism; Interleukin-8 - blood; Lymphocytes T; Metalloendopeptidases; Metalloproteinase; Mice; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; NF-κB; NF-κB protein; Nitric Oxide Synthase Type II - metabolism; Rodents; Sesquiterpenes - therapeutic use; Tumor Necrosis Factor-alpha - metabolism; Tumorigenesis; Zerumbone; BFT; NF-κB; ETBF; zerumbone; inflammation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20184560

Enterotoxigenic
(ETBF) is human intestinal commensal bacterium and a potent initiator of colitis through secretion of the metalloprotease
toxin (BFT). BFT induces cleavage of E-cadherin in colon cells, which subsequently leads to NF-κB activation. Zerumbone is a key component of the
(L.) Smith plant and can exhibit anti-bacterial and anti-inflammatory effects. However, whether zerumbone has anti-inflammatory effects in ETBF-induced colitis remains unknown. The aim of this study was to determine the anti-inflammatory effect of orally administered zerumbone in a murine model of ETBF infection. Wild-type C57BL/6 mice were infected with ETBF and orally administered zerumbone (30 or 60 mg/kg) once a day for 7 days. Treatment of ETBF-infected mice with zerumbone prevented weight loss and splenomegaly and reduced colonic inflammation with decreased macrophage infiltration. Zerumbone treatment significantly decreased expression of IL-17A, TNF-α, KC, and inducible nitric oxide synthase (iNOS) in colonic tissues of ETBF-infected mice. In addition, serum levels of KC and nitrite was also diminished. Zerumbone-treated ETBF-infected mice also showed decreased NF-κB signaling in the colon. HT29/C1 colonic epithelial cells treated with zerumbone suppressed BFT-induced NF-κB signaling and IL-8 secretion. However, BFT-mediated E-cadherin cleavage was unaffected. Furthermore, zerumbone did not affect ETBF colonization in mice. In conclusion, zerumbone decreased ETBF-induced colitis through inhibition of NF-κB signaling.