title: Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells.
abstract: Indirubin, an active ingredient of a traditional Chinese medicine prescription named Danggui Longhui Wan, has been reported to exhibit abroad anti-cancer and anti-inflammation activities. However, the effect of indirubin on ulcerative colitis (UC) has not been addressed. Here, we investigated the therapeutic efficacy of indirubin on dextran sulfate sodium (DSS)-induced UC in mice and explored its underlying mechanisms. UC model was induced in BALB/c mice by administrating with 3% DSS in drinking water for 7days. Subsequently, indirubin treatment (10mg/kg) for 7days obviously inhibited the loss of body weight, reversed the elevation of disease activity index (DAI), alleviated crypt distortion and mucosal injury, and reduced inflammatory cell infiltration in the colon mucosa, thereby ameliorating DSS-induced UC. Mechanically, the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-2 as well as myeloperoxidase (MPO) activity in colon tissues were decreased significantly, while the levels of IL-4 and IL-10 were increased remarkably by indirubin treatment. Moreover, indirubin administration effectively suppressed CD4(+) T cell infiltration in the colon of DSS-induced UC mice and promoted the generation of Foxp3-expressing regulatory T cells. Additionally, further studies showed that indirubin obviously inhibited DSS-induced activation of nuclear factor (NF)-κB signaling. These results reveal that the significant anti-UC effect of indirubin may be attributable to its inhibition of inflammatory responses and promotion of Foxp3(+) T cells. Our studies provide the first evidence for the anti-UC effect of indirubin as well as the related molecular mechanisms and suggest a promising candidate drug for UC therapy.
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China. Electronic address: wen_yan_gao@sina.com.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Xi'an Medical University, Xi'an 710021, People's Republic of China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Sheng
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.
authors.forename: Zhuolin
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China. Electronic address: yang_gong0204@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007211:Indoles; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; C027185:indirubin
keywords: Dextran sulfate sodium (DSS); Foxp3; Indirubin; Inflammation; Nuclear factor-κB; Ulcerative colitis (UC)