Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-?B signaling and T-helper cell homeostasis.

Inflammation research : official journal of the European Histamine Research Society ... [et al.]

PubMedID: 27900412

Chen YY, Li RY, Shi MJ, Zhao YX, Yan Y, Xu XX, Zhang M, Zhao XT, Zhang YB. Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-?B signaling and T-helper cell homeostasis. Inflamm Res. 2016;.
OBJECTIVE
The activation of NF-?B signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-?B pathway and Th cells homeostatis.

METHODS
Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 µM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test.

RESULTS
In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-a (TNF-a), and inhibited the activation of NF-?B signaling pathway. Furthermore, DMB decreased interferon (IFN)-?, increased IL-4 concentration in the mice splenocytes and the ratio of IgG1/IgG2a in the serum. In vitro, ROS production and pro-inflammation cytokines were markedly inhibited by DMB in RAW264.7 cell.

CONCLUSIONS
Our findings revealed that DMB alleviated mice colitis and inhibited the inflammatory responses by inhibiting NF-?B pathway and regulating the balance of Th cells.