Caffeic Acid Ameliorates l -Methionine-Induced Hyperhomocysteinemia, Leading to Decreased Adult Neurogenesis and Oxidative Stress Status in Adult Rats

Abstract Chronic l-methionine (l-met) treatment induces hyperhomocysteinemia, which impairs neurogenesis and memory by increasing oxidative stress. Caffeic acid (CA) possesses antioxidant properties that reduce brain oxidative damage and promote neurogenesis. This study investigated the neuroprotective effects of caffeic acid against the impact of l-met on hippocampal neurogenesis. Forty male Sprague–Dawley rats were randomly assigned to four groups (n = 10 per group): Control, l-met, CA, and CA+l-met. Rats received daily oral gavage of l-met (1.7 g/kg) and/or CA (40 mg/kg) for 28 days. The results demonstrated that CA ameliorated l-met-induced decreases in DCX and Sox-2-positive cells in the SGZ of the dentate gyrus, as shown by immunofluorescence staining. CA also reversed the l-met-induced decreases in hippocampal protein expression of Nrf2, Sox-2, and BDNF, as determined by Western blotting. Furthermore, CA alleviated l-met-induced oxidative damage and decreased antioxidant enzyme activity in the prefrontal cortex (PF) and hippocampus. These findings demonstrate CA’s ability to counteract neurotoxicity induced by l-methionine.