A SMALL MOLECULE FROM GANODERMA LUCIDUM PROTECTS AGAINST CISPLATIN-INDUCED KIDNEY INJURY VIA SUPPRESSING NLRP3/CASPASE-1 RELATED PYROPTOSIS

Abstract

Introduction: Ganoderma lucidum (Lingzhi) is the medicinal fungi traditionally used to promote health and longevity. Previous studies indicate the Ganoderma lucidum potentially boosts the immune system and suppresses the inflammation in vivo and in vitro. Pyroptosis is a highly inflammatory form of programmed cell death. The study aimed to screen molecules against cisplatin-induced kidney injury. Methods: Forty-two molecules were isolated from Ganoderma lucidum and tested by the cell viability assay for screening protective effects. The mouse tubular epithelial cells (mTECs) were pre-treated with small molecules (20-60 mM) for 6 hours, followed by adding cisplatin (25 mM) for 24-48 hours. The molecular mechanisms of attenuating the cisplatininduced kidney injury were further examined. Results: Among 42 molecules, cell viability tests showed that six molecules significantly attenuated cisplatin-induced cytotoxicity in mTECs (p<0.0001). Molecular docking predicted qNFLZ may interact with an upstream protein of the NFkB pathway. The real-time PCR analysis showed that qNFLZ significantly reduced IL-1b and MCP-1. The western-blot analysis indicated qNFLZ suppressed the phosphorylation of NFkB P65, and activation of NLRP3, caspase-1 and Gasdermin D. The findings suggested qNFLZ protects against cisplatin-induced kidney injury via suppressing NLRP3-caspase-1-Gasdermin D pathway. Conclusions: The study demonstrates qNFLZ is a potential molecule to protect against cisplatin-induced kidney injury clinically.