Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.
Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Xuexiu
X
He
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Zhengkai
Z
Wei
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Jingjing
J
Wang
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Jinhua
J
Kou
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Weijian
W
Liu
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Yunhe
Y
Fu
College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.
Zhengtao
Z
Yang
D000818:Animals; D002470:Cell Survival; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016264:Dextran Sulfate; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D015398:Signal Transduction; D000074084:THP-1 Cells / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D044950:Flavanones; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C436748:alpinetin; D016264:Dextran Sulfate; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate