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

• DOI: 10.1007/s00011-016-1005-3
• Publication Date: 2016-11-29T13:19:46Z
• Authors: Ying-Ying Chen; Rui-Yan Li; Mei-Jing Shi; Ya-Xing Zhao; Yan Yan; Xin-Xin Xu; Miao Zhang; Xiao-Tong Zhao; Yu-Bin Zhang
• Keywords: 0301 basic medicine; Berberine; Colon; Dextran Sulfate; Anti-Inflammatory Agents; NF-kappa B; T-Lymphocytes, Helper-Inducer; Inflammatory Bowel Diseases; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; RAW 264.7 Cells; Immunoglobulin G; Animals; Cytokines; Homeostasis; Female; Reactive Oxygen Species; Spleen; Signal Transduction

The activation of NF-κB 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-κB pathway and Th cells homeostatis.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.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-α (TNF-α), and inhibited the activation of NF-κB signaling pathway. Furthermore, DMB decreased interferon (IFN)-γ, 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.Our findings revealed that DMB alleviated mice colitis and inhibited the inflammatory responses by inhibiting NF-κB pathway and regulating the balance of Th cells.