Abstract
The nuclear factor (NF)-κB signaling pathway plays an important role in the initialization and development phase of inflammatory injuries, including inflammatory bowel disease (IBD). Sishen Wan (SSW) is a classic Chinese patent medicine listed in the Chinese Pharmacopoeia, which is usually used to treat chronic colitis; however, it is unclear whether SSW can treat IBD via the NF-κB signaling pathway. In the present study, the therapeutic effect of SSW was demonstrated by the decreased index of colonic weight, macroscopic and microscopic score, and pathological observation in chronic colitis induced by trinitrobenzene sulfonic acid. In colonic mucosa of rats with chronic colitis, SSW reduced the levels of calprotectin and eliminated oxidative lesions; downregulated expression of interferon-γ, interleukin (IL)-1β and IL-17; increased expression of IL-4; and suppressed expression of NF-κB p65, and NF-κB essential modulator (NEMO)-like kinase (NLK). Furthermore, SSW inhibited ubiquitinated NEMO, ubiquitin-activated enzyme, and E2i activation, and phosphorylation of downstream proteins (cylindromatosis protein, transforming growth factor-β-activated kinase and P38). These results show that the therapeutic effects of SSW in chronic colitis were mediated by inhibiting the NEMO/NLK signaling pathway to suppress NF-κB activation.
Highlights
Sishen Wan (SSW) is used to treat chronic colitis, including inflammatory bowel disease (IBD), allergic colitis, and irritable bowel syndrome (IBS)
The level of NLK protein was not obviously changed after treatment of colitis with SSW. These results showed that SSW inhibited ubiquitination of the NF-κB essential modulator (NEMO)/NLK signaling pathway to deactivate nuclear factor (NF)-κB in colonic mucosa from rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis
Experimental colitis induced by TNBS showed the characteristic pathological features of chronic colitis in the colonic mucosa, including ulceration, hyperplasia, and inflammatory cell infiltration
Summary
Sishen Wan (SSW) is used to treat chronic colitis, including inflammatory bowel disease (IBD), allergic colitis, and irritable bowel syndrome (IBS). In China, SSW is a classic prescription in traditional Chinese medicine (TCM) for treatment of colitis and has been used for several thousand years. We have indicated that, in IBD, SSW exerts antioxidant and antiapoptotic activity via the P38 mitogen-activated protein kinase (MAPK) signaling pathway, and regulating the equilibrium between proinflammatory and anti-inflammatory cytokine networks (Liu et al, 2012, 2015a,b; Zhao et al, 2013). The mechanism of action of SSW in treatment of IBD remains mostly unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
