Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitiveimpairments in the rat via exerting anti-oxidative and anti-inflammatoryeffects

Background and Objective: Systemic inflammation during infectious disorders usually accompanies chronic complications including cognitive dysfunction. Neuroinflammation and cognitive deficit are also observed in some debilitating neurological disorders like Alzheimer’s and Parkinson’s diseases. Genistein is a soy isoflavone with multiple beneficial effects including anti-inflammatory and anti-oxidative. In this research, the effect of genistein in prevention of lipopolysaccharide (LPS)-induced cognitive dysfunction was investigated. Materials and Methods: This Experimental study was performed in physiology laboratory in Iran University of Medical Science during 2017.in this study Male Wistar rats (190–230 g, Pasteur’s Institute of Iran) were hold in a laboratory animals’ facility. The rats (n =48) were assigned to 6 experimental groups, i.e. control, LPS, genistein10-, genistein50- and genistein100-treated LPS (receiving genistein at doses of 10, 50, or 100 mg/kg/day), and dexamethasone-treated LPS that injected i.p. This dose of dexamethasone has shown to be effective for sepsis management and its associated memory deficit. Behavioral tests consisting of Y-maze, novel object recognition, and passive avoidance tasks executed at week one following LPS injection. Variables measured in this study were hippocampal oxidative stress-related parameters as: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) also we measured the hippocampal levels of IL-6 and AChE activity. Data collected and analyzed using Sigmaplot Software version12 and also Sigmastat version 3.5. In all analyses, p < .05 was considered significant. Also this study has been approved by the ethical committee (code: Nimad 94352) of Iran University of Medical Sciences (IUMS). Findings: Our results demonstrated that genistein could dose-dependently attenuate spatial recognition (p < 0.01), discrimination (p < 0.005), and memory deficits (p < 0.01). Additionally, genistein treatment of LPS-challenged group lowered hippocampal level of MDA (p < 0.05) and increased activity of SOD (p < 0.05-0.01) and GSH (p < 0.05-.01) level. Furthermore, genistein ameliorated hippocampal AChE activity (p < 0.01) in LPS-challenged rats. Furthermore, genistein administration to LPS-injected group lowered hippocampal level of interleukin 6 (IL-6) (p < 0.005). Conclusion: Our findings suggest that, genistein alleviated LPS-induced cognitive dysfunctions and neural inflammation attenuation of oxidative stress and AChE activity and appropriate modulation of IL-6.

کلیدواژه ها:

Genistein ، Lipopolysaccharide ، Neuroinflammation ، Oxidative stress ، Cognition ، Learning and memory