Abstract
Treatment with valproic acid (VPA) deteriorates hippocampal neurogenesis, which leads to memory impairment. Hesperidin (Hsd) is a plant-based bioflavonoid that can augment learning and memory. This study aimed to understand the effect of Hsd on the impairment of hippocampal neurogenesis and memory caused by VPA. The VPA (300 mg/kg) was administered by intraperitoneal injection twice daily for 14 days, and Hsd (100 mg/kg/day) was administered by oral gavage once a day for 21 days. All rats underwent memory evaluation using the novel object location (NOL) and novel object recognition (NOR) tests. Immunofluorescent staining of Ki-67, BrdU/NeuN, and doublecortin (DCX) was applied to determine hippocampal neurogenesis in cell proliferation, neuronal survival, and population of the immature neurons, respectively. VPA-treated rats showed memory impairments in both memory tests. These impairments resulted from VPA-induced decreases in the number of Ki-67-, BrdU/NeuN-, and DCX-positive cells in the hippocampus, leading to memory loss. Nevertheless, the behavioral expression in the co-administration group was improved. After receiving co-administration with VPA and Hsd, the numbers of Ki-67-, BrdU/NeuN-, and DCX-positive cells were improved to the normal levels. These findings suggest that Hsd can reduce the VPA-induced hippocampal neurogenesis down-regulation that results in memory impairments.
Highlights
Several bioactive compounds found in natural products have multiple therapeutic benefits and biological activities
Effects of Valproic Acid (VPA) and Hesperidin (Hsd) on Memory Evaluated by Novel Object
Effects of valproic acid (VPA) and Hsd on Memory Evaluated by Novel Object Recognition (NOR) Test
Summary
Several bioactive compounds found in natural products have multiple therapeutic benefits and biological activities. Flavonoids in natural, plant-based products have numerous antioxidant activities that degrade reactive oxygen species and provide safeguarding in age-related neurodegenerative disorders, such as dementia [1]. Hesperidin (Hsd) is an important flavonoid that provides numerous biological and health-beneficial effects, including anti-inflammatory properties, antioxidant protection against oxidative stress, radical scavenging, and cytoprotective potential [2,3,4]. A recent, interesting study demonstrated that the neuroprotective effects of Hsd lowered the unwanted effect of methotrexate (MTX) chemotherapy-induced memory impairment by attenuating hippocampal neurogenesis [7]. In addition to MTX chemotherapy, the anticonvulsant drug valproic acid (VPA) can act as an antimitotic agent, diminishing hippocampal neural precursor cell function and causing memory loss [11].
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