Kaempferol Attenuates Cognitive Deficit Regulating Oxidative Stress and Neuroinflammation in an Ovariectomized Rat Model of Sporadic Dementia

Alzheimer's disease (AD) is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present study investigated the effects of kaempferol (Kmp) isolated from the extract of Mespilus germanica L. (medlar) leaves on cognitive impairment, hippocampal antioxidants, apoptosis, lipid peroxidation and neuro-inflammation markers in ovariectomized (OVX) rat models of sporadic AD. Kaempferol, as the main flavonoid of medlar extract has been previously known for anti-oxidative, anti-inflammatory and anti-neurotoxic effects. Thirty-two female Wistar rats were ovariectomized, and randomly divided into four groups: sham, OVX + saline, OVX + streptozotocin (STZ) + saline, OVX + STZ + Kmp. Animals received intracerebroventricular injection of STZ (3 mg/kg, twice with one day interval) to establish models of sporadic AD. Intraperitoneal injection of Kmp (10 mg/kg) for 21 days was performed in the OVX + STZ + Kmp group. Spatial learning and memory of rats were evaluated using a Morris water maze. Finally, brain homogenates were used for biochemical analysis by enzyme-linked immunosorbent assay. The results showed a significant improvement in spatial learning and memory as evidenced by shortened escape latency and searching distance in Morris water maze in the OVX + STZ + Kmp group compared with the OVX + STZ group. Kmp also exhibited significant elevations in brain levels of antioxidant enzymes of superoxide dismutase and glutathione, while reduction in tumor necrosis factor-α and malondialdehyde. Our results demonstrate that Kmp is capable of alleviating STZ-induced memory impairment in OVX rats, probably by elevating endogenous hippocampal antioxidants of superoxide dismutase and glutathione, and reducing neuroinflammation. This study suggests that Kmp may be a potential neuroprotective agent against cognitive deficit in AD.