Abstract
Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.
Highlights
Ulcerative colitis (UC) is one of the most common chronic inflammatory bowel diseases (IBD) which is characterized by dysfunction of the innate and adaptive immunity
An NF-E2-related factor-2 (Nrf2) deficiency causes an exacerbation of inflammation in a variety of murine models, such as sepsis, pleurisy, and emphysema, which indicates that Nrf2 is essential for the control of inflammation and oxidative stress
To investigate the potential antioxidant and anti-inflammatory effects of the maggot extracts, western blot analysis was performed to detect the expression of Nrf2 and HO-1 induced by different concentrations of the maggot extracts in the LPS-stimulated RAW 264.7 cells
Summary
Ulcerative colitis (UC) is one of the most common chronic inflammatory bowel diseases (IBD) which is characterized by dysfunction of the innate and adaptive immunity. UC mostly affects young and middleaged people, and up to 18% of patients suffer from a chronic active disease associated with significant morbidity and loss of productivity, which generally requires lifelong treatment [3]. It is widely believed that the disease pathology is caused by a combination of environmental factors, genetic specificity, inflammation, oxidative stress, and intestinal flora imbalance [4]. Multiple factors such as overproduction of inflammatory mediators including
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