Rosuvastatin Attenuates High-Salt and Cholesterol Diet Induced Neuroinflammation and Cognitive Impairment via Preventing Nuclear Factor KappaB Pathway.

Abstract

Recent attention is focused on the impact of diet on health and mental well-being. High-salt and cholesterol diet (HSCD) is known to be associated with neuroinflammation which is the predominant factor for neurodegenerative disease like Alzheimer disease (AD). In the present study, we examined the neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated that HSCD-induced cognitive impairment as determined by Morris water maze (MWM) task. HSCD also activated nuclear factor kappaB (NF-kB) signaling pathway. The cytokine response was measured using a cytometric bead-based assay quantified by flow cytometry. Treatment with rosuvastatin decreased the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and increased interleukin-10 (IL-10) in a dose-dependent manner. Our results also demonstrated that the rosuvastatin modulates neuronal cell death by inhibiting the overexpression of NF-kB in the CA1 region of hippocampus. In addition, molecular docking study of rosuvastatin indicated high affinity and tighter binding capacity for the active site of the NF-kB. These results suggest that HSCD-triggered inflammatory response and cognitive impairment may be associated with NF-κB signaling pathway. Therefore, treatment with rosuvastatin could be a potential new therapeutic strategy for sporadic dementia of AD.

• Authors: Ibraheem Husain, Mohd Akhtar, Divya Vohora, Malik Zainul Abdin, Mohammad Islamuddin, Mohd Jawaid Akhtar, Abul Kalam Najmi
• Journal: Neurochemical research (Neurochem Res) Vol. 42 Issue 8 Pg. 2404-2416 (Aug 2017) ISSN: 1573-6903 [Electronic] United States
• PMID: 28417263 (Publication Type: Journal Article)

Chemical References

• Cholesterol, Dietary
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Inflammation Mediators
• NF-kappa B
• Sodium Chloride, Dietary
• Rosuvastatin Calcium

Topics

• Animals
• Brain (drug effects, metabolism)
• Cholesterol, Dietary (adverse effects)
• Cognitive Dysfunction (etiology, metabolism, prevention & control)
• Female
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Inflammation (etiology, metabolism, prevention & control)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Maze Learning (drug effects, physiology)
• Molecular Docking Simulation (methods)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Rats
• Rats, Wistar
• Rosuvastatin Calcium (pharmacology, therapeutic use)
• Signal Transduction (drug effects, physiology)
• Sodium Chloride, Dietary (adverse effects)