Plumbagin attenuated oxygen-glucose deprivation/reoxygenation-induced injury in human SH-SY5Y cells by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.
Qianrui ZhangSheng ZhaoWenxia ZhengHaitan FuTao WuFei HuPublished in: Bioscience, biotechnology, and biochemistry (2019)
Plumbagin (PLB), an alkaloid obtained from the roots of the plants of Plumbago genus, is an inhibitor of NADPH oxidase 4 (NOX4). This study aimed to investigate the beneficial effect of PLB against oxygen-glucose deprivation/reoxygenation (OGDR)-induced neuroinjury in human SH-SY5Y neuronal cultures. Our results showed that OGD/R stimulated NOX4 protein expression and reactive oxygen species (ROS) production in SH-SY5Y cells, whereas increased 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) production, resulting in the activation of the NLRP3 inflammasome. And PLB pretreatment reduced the ROS production by regulating the expression of NOX4 and downregulated NF-κB signaling which was induced by OGDR. Furthermore, PLB inhibited OGDR induced NLRP3 inflammasome activation but not PARP1. Overall, PLB improved OGDR induced neuroinjury by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.
Keyphrases
- nlrp inflammasome
- reactive oxygen species
- high glucose
- induced apoptosis
- endothelial cells
- dna damage
- diabetic rats
- signaling pathway
- cell death
- cell cycle arrest
- drug induced
- blood pressure
- endoplasmic reticulum stress
- blood glucose
- cell proliferation
- induced pluripotent stem cells
- inflammatory response
- metabolic syndrome
- blood brain barrier
- pluripotent stem cells