Shahed University

Troxerutin exerts neuroprotection against lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting SIRT1/SIRT3 signaling pathway

Nida Jamali-Raeufy | Sedighe Kardgar | Tourandokht Baluchnejadmojarad | Mehrdad Roghani | Mina Goudarzi
URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=137353
Date :  2019/09/01
Publish in :    Metabolic Brain Disease
DOI :  https://doi.org/10.1007/s11011-019-00454-9
Link :  http://dx.doi.org/10.1007/s11011-019-00454-9
Keywords :Lipopolysaccharide . Neuroinflammation . Oxidative stress . SIRT1 . SIRT3 . Troxerutin

Abstract :
This study was conducted to clarify the potential mechanisms of Troxerutin neuroprotection against Lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting the SIRT1/SIRT3 signaling pathway. To establish a model, a single dose of LPS (500μg/kg bodyweight)was injected tomaleWistar rats intraperitoneally. Troxerutin (100mg/kg bodyweight) was injected intraperitoneally for 5 days after induction of the model. Cognitive and behavioral evaluations were performed using Y-maze, single-trial passive avoidance, and novel object recognition tests. The expression of inflammatory mediators, SIRT1/ SIRT3, and P53 was measured using the ELISA assay. Likewise, the expression levels of SIRT1/SIRT3 and NF-κB were determined using Western blot assay. Brain acetyl-cholinesterase activity was determined by utilizing the method of Ellman. Reactive oxygen species (ROS) was detected using Fluorescent probe 2, 7-dichlorofluorescein diacetate (DCFH-DA). Furthermore, malondialdehyde (MDA) levels were determined. A single intraperitoneal injection of LPS was led to ROS production, acute neuroinflammation, apoptotic cell death, and inactivation of the SIRT1/SIRT3 signaling pathway. Likewise, ELISA assay demonstrated that post-treatment with Troxerutin considerably suppressed LPS-induced acute neuroinflammation, oxidative stress, apoptosis and subsequently memory impairments by targeting SIRT1/SIRT3 signaling pathway. Western blot assay confirmed ELISA results about SIRT1/SIRT3 and NF-κB proteins. These results suggest that Troxerutin can be a suitable candidate to treat neuroinflammation caused by neurodegenerative disorders.