Timosaponin BⅡ alleviates DSS-induced ulcerative colitis in mice by
inhibiting NLRP3
Abstract
Background and Purpose Inhibition of NLRP3 inflammasome plays a critical
therapeutic potential in colonic inflammatory responses. The Timosaponin
BⅡ (TBⅡ) isolated from the traditional Chinese medicine Anemarrhena
asphodeloides has outstanding anti-inflammatory effects in various
diseases. Here, we investigated the protective effects of TBⅡ against
dextran sulfate sodium (DSS)-induced ulcerative colitis in mice.
Experimental Approach Wild-type (WT) and NLRP3 knockout (NLRP3-/-) mice
were applied to evaluate the protective effects of TBⅡ in DSS-induced
mice colitis. The role of TBⅡ in the LPS+ATP-induced cell model was
evaluated by inhibiting or overexpressing NLRP3. RNA-seq, ELISA, western
blots, immunofluorescence staining, and the expression analysis by qPCR
were performed to examine the alterations of colonic NLRP3 expression in
colon tissues and cells, respectively. Key Results TBⅡ treatment
repaired the intestinal mucosal barrier and alleviated colonic
inflammation In mice with DSS-induced ulcerative colitis. RNA-seq
analysis and levels of protein expression demonstrated that TBⅡ could
prominently inhibit NLRP3 signaling. TBⅡ-mediated NLRP3 inhibition was
associated with the alleviation of intestinal permeability and the
inflammatory response via blocking the communication between epithelial
cells and macrophages. However, pharmacological inhibition of NLRP3 or
NLRP3 overexpression significantly impaired TBⅡ-mediated the
anti-inflammatory effect. Mechanistically, TBⅡ-mediated NLRP3 inhibition
may be partially associated with the suppression of NF-κB. Conclusion
and Implications TBⅡ exerted a prominent protective effect against
colitis by impeding the crosstalk between epithelial cells and
macrophages, partially in the NLRP3-mediated inhibitory mechanism. These
beneficial effects could make TBⅡ a promising drug for relieving
colitis.