Picroside II alleviates DSS-induced ulcerative colitis by suppressing the production of NISIP3 inflammasomes through NF-κB signaling pathway

Context: Ulcerative colitis (UC) is a common acute or chronic intestinal disease with an imbalance of inflammation. Picroside II (P-II) exerts a protective role in various inflammation-related diseases. However, the effect of P-II on UC is still unclear. Objective: To explore the effect of P-II on UC and its potential mechanism. Materials and methods: Human monocytic leukemia cell line THP-1 was treated with phorbol ester (PMA) to differentiate into a macrophage. The differentiated THP-1 cells were hatched with LPS combined with ATP or Nigericin to activate the NLRP3 inflammasome in vitro. The UC model was constructed by injection of DSS into mice. Results: The maximum nontoxic concentration of P-II on THP-1 cells was 60 mu M. LPS combined with ATP or Nigericin stimulated the production of IL-1 beta, which was antagonized by P-II treatment. Meanwhile, P-II administration interfered with the aggregation of ASC and the assembly of NLRP3 inflammasomes. Also, P-II treatment reduced the LPS and ATP-induced elevation of the relative protein expression of NLRP3, pro-caspase-1, IL-1 beta and p-p65/p65, and the concentration of TNF-alpha and IL-6. Besides, the NF-kappa B specific inhibitor BAY-117082 notably repressed the LPS together with ATP-enhanced the relative protein expression of NLRP3, caspase-1 and IL-1 beta. Moreover, in vivo results showed that P-II relieved the DDS-induced UC, as evidenced by the improvement of mice weight, DAI and pathological scores. In addition, P-II treatment notably decreased DDS-promoted expression of NLRP3 inflammasomes and inflammatory factors in vivo. Conclusion: P-II alleviated DSS-induced UC by repressing the production of NLRP3 inflammasomes via the NF-kappa B signaling pathway.