the protective effects and underlying mechanisms of kaempferol on sepsis associated cognitive impairment in rats

Objectives: the neuroprotective effects of kaempferol (kmf) have been previously reported; however, its possible effects on sepsis-associated encephalopathy are still unclear. this study aimed to investigate the effects and underlying mechanisms of kmf on cognitive impairment in cecal ligation and puncture (clp)-induced sepsis model.methods: male wistar rats were submitted to clp model. the animals were grouped into the sham, sham + kmf, clp, and clp + kmf groups and treated with kmf (50 mg/kg, i.p). twenty-four hours after clp, the cytokines, nf-kb level, myeloperoxidase (mpo) activity, oxidative damage to lipids and proteins, and antioxidant enzymes activities were evaluated in the hippocampus. 10 days after sepsis induction, behavioral tests were performed to assess the cognitive damage.results: kmf reduced the tnf-α and il-1β levels, mpo activity, protein level of nf-kb, and expression of tlr4 and myd88 in the hippocampus of septic rats. kmf decreased the levels of oxidative stress parameters (mda and protein carbonyls groups) and elevated the activities of the antioxidant enzymes superoxide dismutase (sod), catalase (cat) and glutathione peroxidase (gpx). in addition, the expression level of genes involved in the anti-oxidant defense system such as nuclear factor erythroid 2-related factor 2 (nrf2) and heme oxygenease-1 (ho-1) were upregulated following kmf treatment.conclusion: these findings indicated that kmf exhibited protective effects on the survival rate and cognitive dysfunction after sepsis by inhibiting the inflammatory responses and oxidative stress.