Work

Tetrahydrocurcumin Protects Microglial Cells Against Pseudomonas aeruginosa Lipopolysaccharide-Induced Reactive Oxygen Species Production and Cathepsin B to Activate NLRP3 Inflammasome-Mediated Pyroptosis Via the HO-1 and p38/JNK Pathway

Year: 2025

Type: article

Abstract: Tetrahydrocurcumin (THC), a major curcuminoid metabolite known for its antioxidant and anti-inflammatory properties, has potential for reducing brain inflammation.This study investigated THC's anti-inflammatory responses and molecular mechanisms against Pseudomonas aeruginosa LPS (P.a.LPS)-induced NLRP3 inflammasome and ROS-producing cell pyroptosis.In the current study, we showed that THC significantly attenuated P.a.LPS-induced inflammasome factor IL-18 production through lysosomal dysfunction and leakage of cathepsin B. Importantly, THC reduced the levels of NLRP3 inflammasome and pyroptosis-related proteins, including NLRP3, active caspase-1, ASC, N-GSDMD, and IL-18.We also demonstrate that the inhibition of NLRP3 inflammasome activation by THC is ROS-dependent, via inhibition of H2O2 production, SOD activity, and enhancement of GSH activity.Subsequently, we demonstrated that THC treatment significantly reduced LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and increased heme oxygenase-1 (HO-1) expression in BV-2 cells.Furthermore, we used MAPKs (SB203580, SP600125, and U0126) and HO-1 (SnPP) inhibitors to demonstrate that THC modulated inflammasome-mediated pyroptosis may be related to p38 and JNK MAPK and HO-1-dependent inflammatory signaling.Overall, THC can inhibit ROS-triggered NLRP3 inflammasome-mediated pyroptosis by promoting GSH activity and HO-1 expression via modulating the p38 and JNK signaling pathways in P.a.LPS-treated BV-2 cells.

Source: International Journal of Medical Sciences

DOI: 10.7150/ijms.118252