Kaempferol Protects Against Cerebral Ischemia Reperfusion Injury Through Intervening Oxidative and Inflammatory Stress Induced Apoptosis

The aim of this research is to investigate the potential neuro-protective effect of kaempferol which with anti-oxidant, anti-inflammatory, and immune modulatory properties, and understand the effect of kaempferol on reducing cerebral ischemia reperfusion (I/R) injury in vivo. Male adult Sprague Dawley (SD) rats were pretreated with kaempferol for one week via gavage before cerebral I/R injury operation. We found that kaempferol treatment can reduce the cerebral infarct volume and neurological score after cerebral I/R. Rats were sacrificed after 24 h reperfusion. We observed that kaempferol improved the arrangement, distribution, and morphological structure of neurons, as well as attenuated cell apoptosis in brain tissue via hematoxylin and eosin (H&E) staining, Nissl staining and TUNEL staining. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH) kit analysis, enzyme-linked immunosorbent (ELISA) assay, real-time PCR, Western blot, and immunohistochemical examination indicated that kaempferol mitigated oxidative and inflammatory stress via regulating the expression of proteins, p-Akt, p-GSK-3β, nuclear factor erythroid2-related factor 2 (Nrf-2), and p-NF-κB during cerebral I/R, thus increasing the activity of SOD and GSH, meanwhile decreasing the content of MDA in serum and brain tissue, as well as restoring the expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in vivo. Taken together, this study suggested that kaempferol protects against cerebral I/R induced brain damage. The possible mechanism is related with inhibiting oxidative and inflammatory stress induced apoptosis.