Nobiletin Mitigates D-Galactose-Induced Memory Impairment via Improving Hippocampal Neurogenesis in Mice

by Selleckchem | Nov 05 2023

Memory impairment is a characteristic of brain aging, and it is associated with a decrease in neurogenesis. Therefore, enhancing neurogenesis is a potential method for mitigating brain aging. Nobiletin (NOB) is a natural polymethoxylated flavonoid derived from citrus peels. It acts as an antioxidant, enhances anti-inflammation, and displays neuroprotective properties. However, the mechanism of NOB on brain aging has not been elucidated. In this study, D-galactose-induced aging mice were treated with NOB (100 mg/kg/day) for 10 weeks. NOB administration attenuated D-galactose-induced memory impairment and restored hippocampal neurogenesis, including the number of newborn neurons and neural stem cells in mice. Furthermore, it downregulated the pro-inflammatory mediators IL-1 β, IL-6, and pP65 (by 42.2%, 22.9%, and 46.4% of those in the D-galactose treated group, respectively) in the hippocampus and blocked microglia and astrocyte activation. In vitro, NOB inhibited D-galactose-induced inflammatory responses in BV2 cells, and the conditioned medium prepared from NOB- and D-galactose-co-treated BV2 cells elevated the viability (90.3% of control) and differential ability (94.9% of control) of C17.2 cells, compared to the D-galactose-treated group alone. It was concluded that NOB could restore memory impairment via the improvement of neurogenesis by ameliorating neuroinflammation in the hippocampus. Overall, NOB is a potential candidate neurogenesis enhancer for improving brain function.

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The passage you provided describes a study conducted on mice to investigate the effects of nobiletin (NOB), a natural flavonoid derived from citrus peels, on brain aging. The study used D-galactose-induced aging mice as a model and administered NOB to them for a period of 10 weeks.

The findings of the study indicate that NOB treatment attenuated memory impairment caused by D-galactose and restored neurogenesis in the hippocampus of mice. Neurogenesis refers to the process of generating new neurons and is associated with learning and memory. The study observed an increase in the number of newborn neurons and neural stem cells in the hippocampus following NOB treatment.

Furthermore, NOB administration led to a downregulation of pro-inflammatory mediators, specifically interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and phosphorylated P65 (pP65), in the hippocampus. These pro-inflammatory mediators play a role in neuroinflammation, which is associated with brain aging and cognitive decline. NOB also inhibited the activation of microglia and astrocytes, which are types of immune cells in the brain involved in neuroinflammatory responses.

In vitro experiments using BV2 cells (a microglial cell line) showed that NOB inhibited D-galactose-induced inflammatory responses. Additionally, conditioned medium prepared from BV2 cells treated with NOB and D-galactose showed improved viability and differentiation ability of C17.2 cells, which are neural stem cells, compared to the group treated with D-galactose alone.

Based on the study's findings, the researchers concluded that NOB has the potential to restore memory impairment by enhancing neurogenesis and ameliorating neuroinflammation in the hippocampus. The results suggest that NOB could be a promising candidate for enhancing neurogenesis and improving brain function.

It is important to note that these findings are based on a study conducted in mice, and further research is needed to determine if similar effects can be observed in humans.