The protective effects and underlying mechanisms of Kaempferol on sepsis associated cognitive impairment in rats
Abstract
Objectives: The neuroprotective effects of Kaempferol (KMF) have been previously reported; however, its possible effects on sepsis-associated encephalopathy remain unclear. This study aimed to investigate the effects and underlying mechanisms of KMF on cognitive impairment in a cecal ligation and puncture (CLP)-induced sepsis model.
Methods: Male Wistar rats were subjected to the CLP model. The animals were divided into four groups: sham, sham + KMF, CLP, and CLP + KMF, and treated with KMF (50 mg/kg, i.p.). Twenty-four hours after CLP, the levels of cytokines, NF-κB, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins, and antioxidant enzyme activities were evaluated in the hippocampus. Ten days after sepsis induction, behavioral tests were conducted to assess cognitive damage.
Results: KMF reduced TNF-α and IL-1β levels, MPO activity, NF-κB protein levels, and the expression of TLR4 and MYD88 in the hippocampus of septic rats. KMF decreased oxidative stress parameters (MDA and protein carbonyl groups) and increased the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Additionally, the expression of genes involved in the antioxidant defense system, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), was upregulated following KMF treatment.
Conclusion: These findings indicate that KMF exerts protective effects on survival rate and cognitive dysfunction after sepsis by inhibiting inflammatory responses and oxidative stress