Shionone alleviates NLRP3 inflammasome mediated pyroptosis in interstitial cystitis injury.

Abstract

Shionone is a triterpenoid component derived from the herbal medicine Aster tataricus, and it has been reported to possess marked anti-inflammatory properties. The activation of NLRP3 inflammasome plays an important role in cystitis, and the effect of Shionone on NLRP3 inflammasome-dependent pyroptosis remains unclear. In this study, we established an interstitial cystitis (IC) rat model and SV-HUC-1 cell model with CYP or LPS + ATP treatment to mimic inflammation response and induce NLRP3 inflammasome activation. Shionone treatment significantly attenuated the bladder wet weight, score of edema and hemorrhage, enhanced the viability of SV-HUC-1 cell, decreased the rate of pyroptosis. Moreover, Shionone reduced the expression of NF-κB, NLRP3, ASC, Pro-caspase-1, Caspase-1, GSDMD, GSDMD-N at the mRNA and protein levels both in rat and SV-HUC-1 cell model, demonstrating NLRP3 inflammasome pathway was blocked and pyroptosis degree was reduced. These results indicated that Shionone could alleviate interstitial cystitis in Rat model and enhancing the viability of SV-HUC-1 cells via NF-κB/NLRP3/GSDMD-N pathway, which illustrated that Shionone could be used as a drug candidate for the treatment of interstitial cystitis.

• Authors: Xin Wang, Hao Yin, Ling Fan, Yiqun Zhou, Xiaolong Tang, Xiaojun Fei, Hailin Tang, Juan Peng, Junjun Zhang, Yi Xue, Jianping Luo, Qinglei Jin, Qingjiang Jin
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 90 Pg. 107132 (Jan 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 33223465 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• GSDMD protein, human
• Gsdmd protein, rat
• Inflammasomes
• Intracellular Signaling Peptides and Proteins
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Nlrp3 protein, rat
• Phosphate-Binding Proteins
• Triterpenes
• shionone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Cystitis, Interstitial (immunology, metabolism, pathology, prevention & control)
• Disease Models, Animal
• Female
• Humans
• Inflammasomes (metabolism)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Phosphate-Binding Proteins (genetics, metabolism)
• Pyroptosis (drug effects)
• Rats, Sprague-Dawley
• Signal Transduction
• Triterpenes (pharmacology)
• Urinary Bladder (drug effects, immunology, metabolism, pathology)
• Urothelium (drug effects, immunology, metabolism, pathology)
• Rats