Chrysin mitigates neuronal apoptosis and impaired hippocampal neurogenesis in male rats subjected to D-galactose-induced brain aging.

Oxidative stress-induced neuronal apoptosis is primarily involved in brain aging and impaired hippocampal neurogenesis. Long-term D-galactose administration increases oxidative stress related to brain aging. Chrysin, a subtype of flavonoids, exhibits neuroprotective effects, particularly its antioxidant properties. To elucidate the neuroprotection of chrysin on neuronal apoptosis and an impaired hippocampal neurogenesis relevant to oxidative damage in D-galactose-induced brain aging, male Sprague Dawley rats were allocated into vehicle control, D-galactose, chrysin, and cotreated rats. The rats received their respective treatments daily for 8 weeks. The reactions of scavenging enzymes, protein regulating endogenous antioxidant defense, and anti-apoptotic protein expression were significantly reduced in the hippocampus and prefrontal cortex of the animals receiving D-galactose. Conversely, product of oxidative damage and apoptotic protein expressions were significantly elevated in both cortical areas of the D-galactose group. In hippocampal neurogenesis, significant upregulation of cell cycle arrest and decrease in differentiated protein expression were detected after D-galactose administration. Nevertheless, chrysin supplementation significantly mitigated all negative effects in animals receiving D-galactose. This study demonstrates that chrysin likely attenuates brain aging induced by D-galactose by enhancing scavenging enzyme activities and reducing oxidative stress, neuronal apoptosis, and the impaired hippocampal neurogenesis.

Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model.

l-methionine (L-met) is a substantial non-polar amino acid for normal development. L-met is converted to homocysteine that leads to hyperhomocysteinemia and subsequent excessive homocysteine in serum resulting in stimulating oxidative stress and vascular dementia. Several studies have found that hyperhomocysteine causes neuronal cell damage, which leads to memory impairment. Caffeic acid is a substrate in phenolic compound discovered in plant biosynthesis. Caffeic acid contains biological antioxidant and neuroprotective properties. The neuroprotective reaction of caffeic acid can protect against the brain disruption from hydrogen peroxide produced by oxidative stress. It also enhances GSH and superoxide dismutase activities, which protect against neuron cell loss caused by oxidative stress in the hippocampus. Hence, we investigated the protective role of caffeic acid in hippocampal neurogenesis and cognitive impairment induced by L-met in rats. Six groups of Sprague Dawley rats were assigned including control, L-met (1.7 g/kg/day), caffeic acid (20, 40 mg/kg), and L-met + caffeic acid (20, 40 mg/kg) groups. Spatial and recognition memories were subsequently examined using novel object location (NOL) and novel object recognition (NOR) tests. Moreover, the immunofluorescence technique was performed to detect Ki-67/RECA-1, bromodeoxyuridine (BrdU)/NeuN and p21 markers to represent hippocampal neurogenesis changes. The results revealed decreases in vasculature related cell proliferation and neuronal cell survival. By contrast, cell cycle arrest was increased in the L-met group. These results showed the association of the spatial and recognition memory impairments. However, the deterioration can be restored by co-administration with caffeic acid.

Caffeic Acid Alleviates Memory and Hippocampal Neurogenesis Deficits in Aging Rats Induced by D-Galactose.

Hippocampal neurogenesis occurs throughout life, but it declines with age. D-galactose (D-gal) enhances cellular senescence through oxidative stress leading to neurodegeneration and memory impairment. Caffeic acid (CA) acts as an antioxidant via decreasing brain oxidative stress. This study aims to investigate the advantages of CA in alleviating the loss of memory and neurogenesis production in the hippocampus in aged rats activated by D-gal. Fifty-four male Sprague-Dawley rats were unpredictably arranged into six groups. In the D-gal group, rats were administered D-gal (50 mg/kg) by intraperitoneal (i.p.) injection. For the CA groups, rats received 20 or 40 mg/kg CA by oral gavage. In the co-treated groups, rats received D-gal (50 mg/kg) and CA (20 or 40 mg/kg) for eight weeks. The results of novel object location (NOL) and novel object recognition (NOR) tests showed memory deficits. Moreover, a decline of neurogenesis in the hippocampus was detected in rats that received D-gal by detecting rat endothelial cell antigen-1 (RECA-1)/Ki-67, 5-bromo-2'-deoxyuridine (BrdU)/neuronal nuclear protein (NeuN), doublecortin (DCX) by means of staining to evaluate blood vessel associated proliferating cells, neuronal cell survival and premature neurons, respectively. By contrast, CA attenuated these effects. Our results postulate that CA attenuated the impairment of memory in D-gal-stimulated aging by up-regulating levels of hippocampal neurogenesis.