Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available....

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Bibliographic Details
Published in:Phytotherapy research 2018-09, Vol.32 (9), p.1770-1783
Main Authors: Ma, Jiamei, Yin, Ganghui, Lu, Zibin, Xie, Pei, Zhou, Hongling, Liu, Junshan, Yu, Linzhong
Format: Article
Language:English
Subjects:
Activation
AKT protein
Animals
Antioxidants
Body weight
Body weight loss
Caco-2 Cells
Colitis, Ulcerative - chemically induced
Colitis, Ulcerative - drug therapy
Colon
Cytokines
Dextran
Dextran Sulfate
Disease Models, Animal
Epithelium
Flavonoids - pharmacology
Humans
Hydrogen peroxide
IL-1β
Inflammatory bowel disease
Inflammatory bowel diseases
Interleukin-1beta - metabolism
Interleukin-6 - metabolism
Intestine
Lipopolysaccharides
Macrophages
Macrophages - drug effects
Male
Mice
NF-kappa B - metabolism
Peroxiredoxin
Peroxiredoxin III - metabolism
RAW 264.7 Cells
Reactive oxygen species
Reactive Oxygen Species - metabolism
Signal transduction
Signal Transduction - drug effects
Signaling
Sodium
Superoxide dismutase
Superoxide Dismutase - metabolism
Tumor necrosis factor
Tumor Necrosis Factor-alpha - metabolism
Ulcerative colitis
Weight loss
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Summary:Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available. In this study, we aimed to study how did casticin affect UC by evaluating its effects on dextran sulfate sodium (DSS)‐induced colitis in mice. Our data suggested that casticin attenuated body weight loss, colon length shortening, and pathological damage in the colon of DSS‐treated mice. Casticin decreased reactive oxygen species level and chemocytokines (IL‐1β, IL‐6, TNF‐α) productions in colon tissue. The decreased reactive oxygen species level and suppressed proinflammatory cytokines productions were also confirmed in casticin‐treated LPS‐stimulated RAW264.7 cells and hydrogen peroxide‐treated CACO‐2 cells in vitro. Mechanistically, casticin treatment prevented the profound activation of AKT signaling caused by DSS administration. And casticin inhibited the productions of proinflammatory chemocytokines through downregulating AKT/NF‐κB pathway in macrophages. Meanwhile, data revealed that casticin increased expressions of endogenous antioxidants peroxiredoxin 3 and MnSOD were through activation in FOXO3α signaling by downregulating AKT signaling in colon epithelium cells. Our findings demonstrated that casticin alleviated DSS‐induced UC by increasing the antioxidant enzyme peroxiredoxin 3 and MnSOD expressions, and decreasing the production of proinflammatory chemocytokines through inhibition of AKT signaling.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.6108