Troxerutin exerts neuroprotection against lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting SIRT1/SIRT3 signaling pathway
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 body weight) was injected to male Wistar rats intraperitoneally. Troxerutin (100 mg/kg body weight) 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.
KeywordsLipopolysaccharide Neuroinflammation Oxidative stress SIRT1 SIRT3 Troxerutin
The present study was financially supported by research affairs of Iran University of Medical Sciences.
Compliance with ethical standards
Conflict of interest
Authors have no conflict of interest.
- Amani, Hamed, Ebrahim Mostafavi, Hamidreza Arzaghi, Soodabeh Davaran, Abolfazl Akbarzadeh, Omid Akhavan, Hamidreza Pazoki-Toroudi, and Thomas J Webster. 2018. 'Three-dimensional graphene foams: synthesis, properties, biocompatibility, biodegradability, and applications in tissue engineering'. ACS Biomaterials Science & Engineering, 5: 193–214Google Scholar
- Block ML, Zecca L, Hong J-S (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. J Nature Reviews Neuroscience:8–57Google Scholar
- Esterbauer, Hermann, and Kevin H Cheeseman. (1990).  Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. in Methods in enzymology (Elsevier)Google Scholar
- Ian M (2017) The future of genomic medicine involves the maintenance of sirtuin 1 in global populations. Mol Biol 2:00013Google Scholar
- Jamali-Raeufy N, Roghani M, Ramazi S, Mansouri M (2014) Administration of Salvianolic Acid B Attenuates Learning and Memory Deficits in Diabetic Rats: Involvement of Oxidative Stress. J Basic and Clinical Pathophysiology 2:43–50Google Scholar
- Jamali-Raeufy N, Roghani M, Nikbakht F, Ramazi S, Zavvary F (2015) Salvianolic acid improves status epilepticus and learning and memory deficiency in rat model of temporal lobe epilepsy. J Basic and Clinical Pathophysiology 3:39–46Google Scholar
- Jiang D-Q, Wang Y, Li M-X, Ma Y-J, Wang Y (2017) SIRT3 in neural stem cells attenuates microglia activation-induced oxidative stress injury through mitochondrial pathway. J Frontiers in Cellular Neuroscience 11:7Google Scholar
- Kessler, M, G Ubeaud, T Walter, F Sturm, and L Jung. (2002). Free radical scavenging and skin penetration of troxerutin and vitamin derivatives, J Dermatological Treatment 13: 133–41Google Scholar
- Martins IJ (2018) Bacterial lipopolysaccharides and neuron toxicity in neurodegenerative diseases. Neurol Neurosurg 1:1–3Google Scholar
- Zhào, Hóngyi, Yu Liu, Jing Zeng, Dandan Li, Weiwei Zhang, Yonghua Huang. (2018). Troxerutin and Cerebroprotein Hydrolysate Injection Protects Neurovascular Units from Oxygen-Glucose Deprivation and Reoxygenation-Induced Injury In Vitro, J Evidence-Based Complementary and Alternative Medicine 2018Google Scholar