Phloridzin attenuates lipopolysaccharide-induced cognitive impairment via antioxidant, anti-inflammatory and neuromodulatory activities

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2021-03, Vol.139, p.155408-155408, Article 155408
• Main Authors: Kamdi, Sandesh P., Raval, Amit, Nakhate, Kartik T.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants - metabolism; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - metabolism; Cytokines; Disease Models, Animal; Glutathione - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Lipopolysaccharides - pharmacology; Male; Maze Learning - drug effects; Memory; Memory - drug effects; Memory Disorders - drug therapy; Memory Disorders - metabolism; Mice; Neuroinflammation; Neuroinflammatory Diseases - chemically induced; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - metabolism; Neuroprotective Agents - pharmacology; Neurotransmitter Agents - metabolism; Oxidative Stress - drug effects; Phlorhizin - pharmacology; Phloridzin; Superoxide Dismutase - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2020.155408

[Display omitted] •Lipopolysaccharide (LPS) administration in mice causes memory impairment.•LPS reduces antioxidants and neurotropic factors in the brain.•LPS increases inflammatory markers and cholinesterase activity in the brain.•Phloridzin reverses the biochemical changes induced by LPS.•Phloridzin enhances memory performance of LPS treated mice.•Pholridzin can be used to treat neurodegenerative conditions. Lipopolysaccharide (LPS) is known to produce neuroinflammation and memory impairment. Although phloridzin (a phenolic phytoconstituent) shows antioxidant- and anti-inflammatory activities, its ameliorative potential in LPS-mediated neuroinflammation and memory dysfunction remains unexplored. To investigate the protective effect of phloridzin against LPS-mediated memory impairment and neuroinflammation in mice. Different groups of mice were treated with LPS (250 μg/kg) via intraperitoneal (ip) route to induce cognitive impairments. The animals were administered with phloridzin (10–20 mg/kg, oral) or donepezil (1 mg/kg, intraperitoneal), and memory functions were evaluated by Morris water maze (MWM) and Y-maze. At the end of the behavioral experiments, the animals were sacrificed and different biochemical parameters like acetylcholinesterase (AChE), brain derived neurotropic factor (BDNF), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD) and glutathione (GSH) concentration in the hippocampus and the cerebral cortex were estimated. While LPS administered animals showed significantly decreased memory retention in both MWM and Y maze, a significant reversal in all the parameters were observed following treatment with phloridzin. LPS-treated animals showed significantly decreased level of antioxidants (SOD and GSH), neurotropic factor (BDNF) and cholinergic transmission (increased AChE) and increased levels of inflammatory/oxidative markers (TNF-α, IL-6 and MDA) in hippocampus and cortex. These changes were alleviated after the treatment with phloridzin. Phloridzin may have neuroprotective role against LPS-induced neuroinflammation and memory impairment by virtue of its antioxidant, anti-inflammatory, and enhanced cholinergic signalling activity in the hippocampus and cerebral cortex.