Abstract
Background The flower of Abelmoschus manihot (AM) has been widely used in the treatment of chronic inflammatory diseases, including ulcerative colitis. This paper aimed to confirm the therapeutic effect of AM on ulcerative colitis (UC) and explore its mechanism. Methods Mouse models were induced by 2.5% dextran sulfate sodium (DSS) and treated with AM. UC signs, symptoms, colon macroscopic lesion scores, and disease activity index (DAI) scores were observed. Colon levels of interleukin- (IL-) 6, IL-1β, IL-18, IL-17, tumor necrosis factor- (TNF-) α, and IL-10 were quantified by ELISA. The colon protein expression levels of NLRP3, ASC, caspase 1 p10, β-arrestin1, ZO-1, occludin-1, and claudin-1 were examined by immunohistochemistry and western blotting. The mRNA levels of IL-1β, IL-18, NLRP3, ASC, and caspase 1 p10 in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). Results After treatment with AM, the mortality of mice, pathological damage to the colon, splenomegaly, and the spleen coefficient were decreased. AM reduced the levels of proinflammatory cytokines (IL-6, IL-1β, IL-18, IL-17, and TNF-α) and increased the level of IL-10. The mRNA expression levels of NLRP3, ASC, and caspase 1 in colon tissue were decreased by AM in a dose-dependent manner. In addition, AM also reduced the protein expression of NLRP3, ASC, caspase 1 p10, IL-1β, IL-18, and β-arrestin1 in the colon tissue of model mice. Western blot analysis confirmed that AM increased the expression of occludin-1, claudin-1, and ZO-1 in a dose-dependent manner. Conclusion This study shows that AM has a significant therapeutic effect on mice with UC, and the mechanism may be related to the inhibition of the β-arrestin1/NLRP3 inflammasome signaling pathway and the protection of intestinal barrier function.
Highlights
Ulcerative colitis (UC) is a common chronic intestinal inflammatory disease and is a difficult digestive system disease [1, 2]. e clinical symptoms of the patients are often fatigue, increased frequency of bowel movements, mucus discharge, nighttime bowel movements, and abdominal discomfort [1, 3]
It was observed that 7 days of drinking a 2.5% dextran sulfate sodium (DSS) solution ad libitum resulted in a significant reduction in body weight in the mice (Figure 1(b)), decreased food and water intake (Figures 1(c) and 1(d)), and increased mortality (Figure 1(e)). e disease activity index (DAI) increased compared to that in the normal group (Figure 1(f ))
Ere is evidence to support that the NLRP3 inflammasome [32] and intestinal mucosal barrier [13, 14] are related to UC
Summary
Ulcerative colitis (UC) is a common chronic intestinal inflammatory disease and is a difficult digestive system disease [1, 2]. e clinical symptoms of the patients are often fatigue, increased frequency of bowel movements, mucus discharge, nighttime bowel movements, and abdominal discomfort [1, 3]. People with genetic susceptibility to UC exhibit activated immune systems due to antigen stimulation, the interactions of various environmental factors, and a series of abnormal immune responses, thereby causing intestinal inflammation, and the dysregulation of immune function plays an important role in the development of UC [1]. Evidence-Based Complementary and Alternative Medicine e weakened innate immune system of UC patients causes the accumulation of bacterial antigens and stimulates a cascade inflammatory response in the acquired immune system. E NLRP3 inflammasome has a proinflammatory effect during the onset of colitis. Treatment with the NLRP3-dependent procaspase 1, IL-1β, and the IL-18 inhibitor Fclla-2 can reduce colon inflammation in mice [10], and the NLRP3 inflammasome can initiate and promote the inflammatory response in colitis [11]
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