title: Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons.
abstract: Norisoboldine (NOR), the main active constituent of Radix Linderae, was previously demonstrated to ameliorate collagen-induced arthritis in rats through regulating the imbalance of T cells in intestines, which implied its therapeutic potential in inflammatory bowel disease. Here, we investigated the effect of NOR on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice. Results showed that NOR (20, 40mg/kg) markedly reduced the symptoms of colitis, the levels of IL-1β and TNF-α, and the activation of ERK, p38 MAPK and NF-κB-p65. NOR only slightly decreased the levels of IFN-γ and IL-17A in mouse colons, but it dramatically increased the level of IL-10 at both protein and mRNA grades. Consistently, NOR increased the number of CD4(+)CD25(+)Foxp3(+) Treg cells more obviously than it decreased that of CD4(+)IL-17(+) Th17 cells in mesenteric lymph nodes (MLNs) and colonic lamina proprias (LPs) of colitis mice, and promoted the expression of Foxp3 mRNA in colon tissues. It could facilitate the in vitro differentiation of Treg cells from naive T cells and promote the phosphorylations of Smad2/3 in colon tissues of colitis mice. On the other hand, NOR did not affect the expressions of homing receptors CCR9 and α4β7 in SPs, and homing ligands CCL25 and Madcam-1 in MLNs and colonic LPs, suggesting that the increase of Treg cells in colons by NOR was not due to gut homing. In conclusion, NOR can ameliorate DSS-induced UC in mice, and the mechanisms involve reduction of pro-inflammatory cytokines and selective induction of Treg cells in colons.
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Si-Miao
authors.initials: SM
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Can
authors.initials: C
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Xia
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Gui-Xin
authors.initials: GX
authors.lastname: Chou
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: yuedaicpu@hotmail.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: zhifeng-wei@hotmail.com.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Wei
mesh_terms: D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C464745:norisoboldine; D016264:Dextran Sulfate
keywords: Differentiation; Norisoboldine; Pro-inflammatory cytokines; Regulatory T cells; Ulcerative colitis