Andrographolide sulfonate ameliorates experimental colitis in mice by inhibiting Th1/Th17 response.
Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting condition of inflammation involves overproduction of pro-inflammatory cytokines and excessive functions of inflammatory cells. However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma. Therefore new therapies for the treatment of IBD are desperately needed. In the present study, we aimed to examine the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on murine experimental colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Andrographolide sulfonate was administrated through intraperitoneal injection to mice with TNBS-induced colitis. TNBS-induced body weight loss, myeloperoxidase activity, shortening of the colon and colonic inflammation were significantly ameliorated by andrographolide sulfonate. Both the mRNA and protein levels of pro-inflammatory cytokines were reduced by andrographolide sulfonate administration. Moreover, andrographolide sulfonate markedly suppressed the activation of p38 mitogen-activated protein kinase as well as p65 subunit of nuclear factor-κB (NF-κB). Furthermore, CD4(+) T cell infiltration as well as the differentiation of Th1 (CD4(+)IFN-γ(+)) and Th17 (CD4(+)IL17A(+)) subset were inhibited by andrographolide sulfonate. In summary, these results suggest that andrographolide sulfonate ameliorated TNBS-induced colitis in mice through inhibiting Th1/Th17 response. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Wen
W
Liu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Wenjie
W
Guo
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Lele
L
Guo
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yanhong
Y
Gu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Peifen
P
Cai
Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, China.
Ning
N
Xie
Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, China.
Xiaoling
X
Yang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yongqian
Y
Shu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China. Electronic address: wuxf@nju.edu.cn.
Xuefeng
X
Wu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China. Electronic address: yangsun@nju.edu.cn.
Yang
Y
Sun
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China. Electronic address: molpharm@163.com.
Qiang
Q
Xu
D000476:Alkanesulfonates / Q000737:chemistry; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage* / Q000737:chemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000476:Alkanesulfonates; D016207:Cytokines; D004224:Diterpenes; D016328:NF-kappa B; C030419:andrographolide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases
Andrographolide; Colitis; Sulfonate; TNBS; Th1/Th17