Protective effects of Polygalae root in experimental TNBS-induced colitis in mice

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Abstract

In this study, the protective effect of Polygalae root was evaluated in a murine model of experimental colitis by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Polygalae root, given orally at 2, 4 g/kg body weight of herbs once a day consecutively for 9 days, could recover the lost body weight and decrease the gross rectal bleeding. Polygalae root also reduced the degree of inflammation and improved significantly the histological changes such as infiltration by polymorphonuclear leukocytes and multiple erosive lesions. Furthermore, the cytokine production of intraepithelial lymphocytes was analyzed. The results showed that IFN-γ was increased, but IL-4 was decreased in TNBS-induced colitis, when those were compared with the sham controls. But the administration of Polygalae root to TNBS-induced colitis mice showed lower production of IFN-γ and higher production of IL-4 than the TNBS-induced colitis. These results suggest that the protective effects of Polygalae root against the TNBS colitis may be associated with the regulation of cytokine production of intraepithelial lymphocytes.

Introduction

The inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease, are major chronic inflammatory diseases of the gastrointestinal tract in humans. The pathogenesis and molecular biological mechanism are not yet elucidated. The etiology of IBD is very complicated, and is considered to be multifactorial. Several reports have been revealed that immune system plays a critical role in the development and persistence of ulcerative colitis and Crohn's disease (Podolsky, 1991, Strober and Neurath, 1995, Neurath et al., 1995). Especially, some cytokines are closely related to inflammation and regulation of immune response. It has been hypothesized that IBD may be due to imbalance of proinflammatory cytokine such as IL-1 (Reinecker et al., 1993), IL-2 (Murata et al., 1995), IL-6 (Reinecker et al., 1993, Murata et al., 1995), IL-8 (Daig et al., 1996), IFN-γ (MacDonald et al., 1990) and anti-inflammatory cytokines such as IL-4 (West et al., 1996).

Various animal models of intestinal inflammation have recently been established, and these can lead to provide new insights into the pathogenesis and immune response of IBD. Colitis induced by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS) is a model, in which the inflammatory cytokine response has been shown to be mediated by Th1 cells producing IFN-γ (Elson et al., 1996, Qiu et al., 1999), and the neutralization of IL-12 after induction of chronic TNBS colitis has been shown to reduce inflammation and induce recovery of weight (Neurath et al., 1995).

Polygalae root (Polygala tenuifolia Willdenow) is a Kampo herbal medicine prescribed ethically in China and Japan. It has been shown to have the power to suppress stress ulcer in clinic, but the anti-inflammatory activity of it has not been studied. In order to clarify these anti-inflammatory mechanisms, we examined the protective effects of Polygalae root in TNBS-induced colitis in mice.

Section snippets

Plant material and water extract

Polygalae root (Uchida Co., specimen: voucher herbarium specimen number 252228) were obtained from Uchida Wakan Yaku Co. Ltd. (Tokyo, Japan). Fifty gram of crude herb was boiled with 1000 ml of distilled water until the volume was reduced to 600 ml. The supernatant fluid was filtered and lyophilized. The yield of Polygalae root was 21.3% (w/w) in terms of the dried medical herbs. Polygalae root was given orally to mice once a day consecutively for 9 days, and equal volume water was orally given

Effects on general condition of mice with colitis

We found that BALB/c mice subjected to intracolonic administration of TNBS regularly developed colitis with severe diarrhea and rectal prolapse accompanied by extensive wasting disease. Gross blood adhesion to the anus was noted in some mice. After administration of TNBS, the body weight began to decrease, and continued to lower significantly until the ninth day. However, administration of Polygalae roots at doses of 2, 4 g/kg to TNBS colitis mice significantly recovered the lost body weight (

Discussion

In this study, we evaluated the efficacy of Polygalae root in TNBS-induced colitis. Polygalae root, which was orally administered only once soon after TNBS was administrated at doses of 2, 4 g/kg, showed no improvement of TNBS-induced colitis on the 9th day from TNBS was firstly administrated (data not be shown). But if Polygalae root, given orally at 2, 4 g/kg body weight of herbs once a day consecutively for 9 days from the day of treatment with TNBS. The results showed that Polygalae root

Acknowledgements

This work was supported in part by a grant and aid from Tsumura Co.

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