Pharmacological Evaluation of Shogaol on Inflammatory Markers in Mice Model of High Fat Diet and Metals Induced Neuroinflammation

Abstract

VI ABSTRACT Neuroinflammation is complex pathological event in the central nervous system and spinal cord that involves the immune cells of the CNS including microglial and astrocytes cells. Humans are continuously exposed to metals from their surroundings and it is the prime cause of neuroinflammation. Neuroinflammation possess a key role in the progression of several neurodegenerative diseases. High fat diet intake is associated with obesity, cognitive dysfunction, ROS production which represent chronic inflammation. Upregulation of systemic inflammation due to high fat diet intake can recruit inflammatory mediators that can over-come the blood-brain barrier (BBB) and disrupt its functioning. Aluminium (Al), lead (Pb) and arsenic (As) are the most neurotoxic metals causing more harmful effects on the CNS when acting together than alone. The key objective of this study was to evaluate the anti-inflammatory role of Shogaol on metals+HFD associated BBB disruption and inflammatory cytokines. This study is designed to evaluate the effect of metals (Al, As, Pb) and HFD in mice model, 44 male BALB/c were divided into four group (n=11); Group1 (control), Group 2 (metals+ HFD), Group 3 (metals+HFD +Shogaol 2mg/kg) and Group 4 (metals+HFD+Shogaol 12mg/kg) Blood brain barrier assay was performed to check the blood brain barrier permeability induced by metals+HFD and the anti-inflammatory effect of Shogaol on the BBB. Quantitative expression analysis of the inflammatory markers (IL-1 beta, TNF-α and GFAP) was carried out in the cortex and hippocampus; it was found that metals+HFD significantly upregulated these inflammatory genes while Shogaol has the potential to normalize these inflammatory markers. However, further verification of the toxicity mechanisms underlying heavy metals and HFD is needed to further validate the result.