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Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons.
Int Immunopharmacol 2015; 29(2):787-797II

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+Show Affiliations

State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.State Key Laboratory of Natural Medicine, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26363976

Citation

Lv, Qi, et al. "Norisoboldine Ameliorates DSS-induced Ulcerative Colitis in Mice Through Induction of Regulatory T Cells in Colons." International Immunopharmacology, vol. 29, no. 2, 2015, pp. 787-797.
Lv Q, Qiao SM, Xia Y, et al. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. Int Immunopharmacol. 2015;29(2):787-797.
Lv, Q., Qiao, S. M., Xia, Y., Shi, C., Xia, Y. F., Chou, G. X., ... Wei, Z. F. (2015). Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. International Immunopharmacology, 29(2), pp. 787-797. doi:10.1016/j.intimp.2015.08.040.
Lv Q, et al. Norisoboldine Ameliorates DSS-induced Ulcerative Colitis in Mice Through Induction of Regulatory T Cells in Colons. Int Immunopharmacol. 2015;29(2):787-797. PubMed PMID: 26363976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. AU - Lv,Qi, AU - Qiao,Si-Miao, AU - Xia,Ying, AU - Shi,Can, AU - Xia,Yu-Feng, AU - Chou,Gui-Xin, AU - Wang,Zheng-Tao, AU - Dai,Yue, AU - Wei,Zhi-Feng, Y1 - 2015/09/10/ PY - 2015/07/15/received PY - 2015/08/26/revised PY - 2015/08/31/accepted PY - 2015/9/14/entrez PY - 2015/9/14/pubmed PY - 2016/9/22/medline KW - Differentiation KW - Norisoboldine KW - Pro-inflammatory cytokines KW - Regulatory T cells KW - Ulcerative colitis SP - 787 EP - 797 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 29 IS - 2 N2 - 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. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/26363976/Norisoboldine_ameliorates_DSS_induced_ulcerative_colitis_in_mice_through_induction_of_regulatory_T_cells_in_colons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(15)30099-0 DB - PRIME DP - Unbound Medicine ER -