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Efficacy of Wogonin in the Production of Immunoglobins and Cytokines by Mesenteric Lymph Node Lymphocytes in Mouse Colitis Induced with Dextran Sulfate Sodium

2004-09-07 00:01:06

Bioscience, Biotechnology, and Biochemistry; Volume 68, Issue 12, 2004; DOI: 10.1271/bbb.68.2505



Beong Ou Lim



Abstract



We previously examined wogonin, isolated from Scutellaria baicalensis, chemical mediators, and IgE by mesenteric lymph node (MLN) lymphocytes in rats. The present study explores the effect of wogonin on the MLN lymphocyte function of mice given orally at 20 mg/kg for 2 weeks with dextran sulfate sodium (DS)-induced colitis. The results indicate that IgA levels in MLN lymphocytes were high, while IgE was low, in mice given wogonin compared to those given water. Also, fecal IgA concentration of DS in the wogonin group mice was significantly higher than in the DS group. Concentrations of interferon-? and interleukin (IL)-2 of T cells by concanavalin A treatment was significantly higher in the wogonin fed group than in the normal group. Activation-induced IL-4, IL-5 and IL-10 secretion was lower in wogonin fed mice compared control mice after DS-induced colitis. For these reasons, we conclude that wogonin can alleviate the inflammation in DS-induced colitis brought about by an abnormal Th2 response.



INTRODUCTION



Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) is a chronic, relapsing, and remitting condition of unknown origin that exhibits various features of immunological inflammation and affects at least in 1 in 1,000 people in western countries. There is an increasing amount of evidence that the immune system plays a critical role in the development and perpetuation of UC and CD. Studies in humans have implicated impaired mucosal barrier function, pronounced innate immunity, production of proinflammatory and immunoregulatory cytokines,
and the activation of CD4þ T cells in the pathogenesis of IBD. There is clear evidence supporting a role for cytokine in the initiation and perpetuation of IBD. Recent studies have shown that
the production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-1, IL-6, and IL-8 at sites of inflammation is markedly enhanced in patients with UC and CD. Therapeutic trials of cytokine manipulation in such patients further support the idea that cytokines are important in the pathophysiology of these diseases.



Sulfasalazine (Sulf) has been mainly used for the treatment of UC, but the side effects remain a major clinical problem. Chinese herbal medicine has recently been of increased interest for the treatment of these disorders. Scutellaria radix has long been used as the chinese medicine or as a medical plant in oriental countries for various purposes. It has been reported that Scutellaria baicalensis has diverse pharmacological effects. We reported that wogonin extracted from Scutellaria baicalensis has very potent antioxidative action in vivo as well as in vitro. But the study
of the IBD of wogonin has not been totally appreciated. We therefore examined the effect of wogonin administration on IBD using mesenteric lymph node (MLN) lymphocytes isolated from Balb/c mice.



Many studies have shown that chinese medicine has an important role for intestinal structure and function, but very few studies have focused on the effects of wogonin on chemotherapeutic-induced colitis. The purpose of this current study was to evaluate the intestinal immunoregulatory effects of wogonin on DS induced colitis in mice. Oral administration of DS in mice induces colitis resembling human UC. This model corresponds well to the clinical signs of IBD in humans and can serve as a reliable model for studies of this disease. In the present study, we focused on the response of MLN lymphocytes in mice after DS-induced colitis, and found a significant effect of wogonin on Ig, T cell and cytokine production as compared with the DS group.



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Key Words



Wogonin | IgE and IgA | Inflammatory bowel disease | Cytokines | Mesenteric lymph node