Dihydroquercetin ameliorates LPS-induced neuroinflammation and memory deficit

Abstract

Dihydroquercetin (DHQ) is a pentahydroxyflavanone that has been used as an important suppliment against oxidative stress related inflammation and neuroinflammation. Neuroinflammation, which is the activation of the defense mechanism of the central nervous system, upon exposure to stimuli like amyloid β, Lewy bodies, lipopolysaccharide (LPS) and reactive oxygen species. It is an important pathophysiological mediator of a number of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis and others. The objective of the present study is to evaluate the neuroprotective effect of DHQ, a potent antioxidant molecule, against LPS induced neuroinflammation. On the first day of the experiment (day-1), neuroinflammation was induced through intracerebroventricular injection of LPS (5 ​μg/5 μl) into each lateral ventricle in the rats. DHQ-0.5, 1 and 2 ​μg/kg was injected into the tail vein in respective groups from day-2 to day-10. Behavioral studies showed that DHQ attenuated the LPS-induced loss in long-term memory and working memory as evaluated by elevated plus maze and Y-maze test, respectively.Further, the biochemical estimations revealed that DHQ dose-dependently attenuated the LPS-induced decrease in acetylcholine level and increased in the acetylcholine-esterase activity in the hippocampal region. DHQ also increased the catalase activity and decreased nitric oxide and lipid peroxidation altered by LPS injection. DHQ also attenuated interleukin-6 in the brain, which has elevated upon LPS induction. The decrease in IL-6 is attributed to its antioxidant activity. Hence, DHQ could be a potential therapeutic candidate in the management of neuroinflammation and related neurodegenerative disorders.

Keywords

• Dihydroquercetin
• Neurodegenerative disease
• Learning and memory
• Neuroinflammation
• Intracerebroventricular injection