Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia

Abstract

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.

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice

“…Meanwhile, phytochemical analysis of the KBD extract by HPLC fingerprint method revealed the presence of piperine (1), madecassoside (2), asiaticoside (3), quercetin (4), kaempferol (5), kaempferol-3-glucoside (6), rutin 7, luteolin-7-O-glucoside (8), and ferulic acid (9). The radical scavenging and antioxidant activities of these compounds have been extensively reported [35][36][37][38]. Moreover, accumulating evidences suggested that these dietary phytochemicals potently strengthen the antioxidative potential through the modulation of the Nrf2/antioxidant responsive element (ARE) signaling pathway [39][40][41][42].…”

Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders

“…It enhances cognition and memory by uplifting antioxidant defense system, cholinergic signaling, and synaptic plasticity (Ishola et al, 2019). Kaempferol attenuates cognitive deficit through regulating antioxidants and neuro-inflammation (Kouhestani et al, 2018), promotes memory retention and density of hippocampal CA1 neurons (Darbandi et al, 2016). The flavonoid, quercetin has potential therapeutic benefit in AD.…”

Kaempferol Facilitated Extinction Learning in Contextual Fear Conditioned Rats via Inhibition of Fatty-Acid Amide Hydrolase

“…It is reported to be particularly effective against ailments involving inflammation [ 27 ], cancer [ 28 ], and oxidative stress [ 29 ] through modulation of molecular pathways such as NF-kB, PI3k/AKT, MAPK, Bcl2, Caspase 3, and VEGF [ 30 ]. It is of note that kaempferol is capable of exerting beneficial effects against central nervous system disorders as well, such as depression [ 31 ], anxiety [ 32 ], and cognitive deficit [ 33 ]. Keeping in view the aforementioned reports, the present study was designed to observe the effect of kaempferol on fear memory processing and associated anxiety in the context of eCB modulation.…”