Picroside II alleviates DSS-induced ulcerative colitis by suppressing the production of NLRP3 inflammasomes through NF-κB signaling pathway

Abstract

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 μM. LPS combined with ATP or Nigericin stimulated the production of IL-1β, 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-1β and p-p65/p65, and the concentration of TNF-α and IL-6. Besides, the NF-κB specific inhibitor BAY-117082 notably repressed the LPS together with ATP-enhanced the relative protein expression of NLRP3, caspase-1 and IL-1β. 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-κB signaling pathway.

Keywords:

• Ulcerative colitis
• picroside II
• inflammation
• NLRP3 inflammasomes
• NF-κB

Author contributions

HY: Conceptualization, Investigation and Data curation; JY: Writing-Original draft preparation and Methodology; LY: Visualization and Software; WC: Supervision, Validation, Writing-Reviewing and Editing; Approval of final manuscript: All authors.

Disclosure statement

The authors declare that there is no conflict of interest.