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. 2014:2014:569587.
doi: 10.1155/2014/569587. Epub 2014 Jul 10.

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair

Yongbiao Hao  1 , Kazuko Nagase  2 , Kazutoshi Hori  2 , Shenglan Wang  3 , Yoko Kogure  4 , Ken Fukunaga  2 , Shinichiro Kashiwamura  5 , Satoshi Yamamoto  6 , Shiro Nakamura  2 , Junxiang Li  7 , Hiroto Miwa  8 , Koichi Noguchi  9 , Yi Dai  10
Affiliations

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair

Yongbiao Hao et al. Evid Based Complement Alternat Med. 2014.

Abstract

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

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Figures

Figure 1
Figure 1
XLS attenuated DSS-induced colonic mucosal damage in rats. (a) Water + saline (sterile tap water and saline); (b) water + XLS (sterile tap water and 0.3 g XLS); (c) DSS + saline (4% DSS and saline); (d) DSS + XLS (4% DSS and 0.3 g XLS) (HE staining, ×40 and ×400 original magnification); and (e) total histological damage score. Numbers in brackets represent the sample numbers of each group. **P < 0.01 versus water + saline.
Figure 2
Figure 2
XLS reduced colonic MPO activity in DSS-treated rats. Numbers in brackets represent the sample numbers of each group. **P < 0.01 versus water + saline, ## P < 0.01 versus DSS + saline.
Figure 3
Figure 3
In rats, XLS suppressed the increase of a colonic cytokine of IL-1β (a) induced by DSS. IL-6 (b), IL-17 (c), and TNF-α (d) remained constant in DSS group compared with water group, which was comparable to that of XLS groups. Numbers in brackets represent the sample numbers of each group. **P < 0.01 versus water + saline, ## P < 0.01 versus DSS + saline.
Figure 4
Figure 4
In rats, XLS inhibited the increase of the colonic chemokines (a) GRO/KC and (b) MCP-1 induced by DSS. Numbers in brackets represent the sample numbers of each group. **P < 0.01 versus water + saline, ## P < 0.01 versus DSS + Saline.
Figure 5
Figure 5
In rats, XLS upregulated colonic mucosal repair-related cytokine expression of (a) VEGF and (b) MIP-3α. Numbers in brackets represent sample numbers of each group. **P < 0.01 versus water + saline, *P < 0.05 versus water + saline, # P < 0.05 versus DSS + saline, && P < 0.01 versus water + saline, and $$ P < 0.01 versus DSS + XLS.
Figure 6
Figure 6
XLS stimulated enterocyte proliferation in DSS-treated rats. (a) Water + saline; (b) water + XLS; (c) DSS + saline; and (d) DSS + XLS (immunohistochemistry, ×40 and ×400 original magnification). (e) Cell proliferation was evaluated by LI, representative of the immunoreactivity of Ki-67 in colon sections. Numbers in brackets represent sample numbers of each group. **P < 0.01 versus water + saline, && P < 0.01 versus water + saline, and $ P < 0.05 versus DSS + XLS.
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