Tags

Type your tag names separated by a space and hit enter

Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells.
Acta Histochem 2016; 118(6):606-614AH

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+Show Affiliations

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.Department of Pathophysiology, School of Basic Medical Sciences, Xi'an Medical University, Xi'an 710021, People's Republic of China.Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.Department of Traditional Chinese Medicine, The General Hospital of Shenyang Military Area Command, Shenyang 110016, People's Republic of China.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27396532

Citation

Gao, Wenyan, et al. "Indirubin Ameliorates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice Through the Inhibition of Inflammation and the Induction of Foxp3-expressing Regulatory T Cells." Acta Histochemica, vol. 118, no. 6, 2016, pp. 606-614.
Gao W, Guo Y, Wang C, et al. Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells. Acta Histochem. 2016;118(6):606-614.
Gao, W., Guo, Y., Wang, C., Lin, Y., Yu, L., Sheng, T., ... Gong, Y. (2016). Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells. Acta Histochemica, 118(6), pp. 606-614. doi:10.1016/j.acthis.2016.06.004.
Gao W, et al. Indirubin Ameliorates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice Through the Inhibition of Inflammation and the Induction of Foxp3-expressing Regulatory T Cells. Acta Histochem. 2016;118(6):606-614. PubMed PMID: 27396532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells. AU - Gao,Wenyan, AU - Guo,Yufang, AU - Wang,Changhong, AU - Lin,Yifan, AU - Yu,Li, AU - Sheng,Tianjiao, AU - Wu,Zhuolin, AU - Gong,Yang, Y1 - 2016/07/07/ PY - 2016/02/16/received PY - 2016/06/19/revised PY - 2016/06/20/accepted PY - 2016/7/12/entrez PY - 2016/7/12/pubmed PY - 2017/1/24/medline KW - Dextran sulfate sodium (DSS) KW - Foxp3 KW - Indirubin KW - Inflammation KW - Nuclear factor-κB KW - Ulcerative colitis (UC) SP - 606 EP - 614 JF - Acta histochemica JO - Acta Histochem. VL - 118 IS - 6 N2 - 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. SN - 1618-0372 UR - https://www.unboundmedicine.com/medline/citation/27396532/Indirubin_ameliorates_dextran_sulfate_sodium_induced_ulcerative_colitis_in_mice_through_the_inhibition_of_inflammation_and_the_induction_of_Foxp3_expressing_regulatory_T_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0065-1281(16)30134-9 DB - PRIME DP - Unbound Medicine ER -