Chlorogenic acid ameliorates memory dysfunction through reducing oxidative stress, inflammation, and apoptosis in the hippocampus of diabetic rat model

Abstract Objectives Diabetes mellitus (DM) is characterised by extended inflammation and oxidative stress, leading to hippocampal neuronal apoptosis and memory dysfunction. Antioxidant and neuroprotective effects have been identified in chlorogenic acid (CGA). However, its function in hippocampal pathology under diabetic conditions remains unclear. This study was conducted to examine the function of CGA in attenuating memory dysfunction and its possible mechanisms in hyperglycaemic rats. Methods Male Wistar rats were injected with a single intraperitoneal injection of streptozotocin and divided into two groups: DM1.5, observed for 1.5 months, and DM2, observed for 2 months. The rats were injected with different doses of CGA into the abdominal cavity. The injections were administered from 1.5 to 2 months at doses of 12.5 mg/kg (CGA1), 25 mg/kg (CGA2), and 50 mg/kg (CGA3). The study also included a control group. Memory function was assessed using the Morris water maze (MWM) before termination. Blood samples and hippocampal tissues were collected for RNA extraction and histopathological analysis. Results The DM1.5 and DM2 groups exhibited longer acquisition path lengths and ELT in the MWM test. These outcomes were associated with increased mRNA expression of TNF-α, NFκB, p53, and Bax, and decreased mRNA expression of SOD2 and Bcl-2 compared with the control group. The CGA1 group illustrated improved memory performance, lower TNF-α, NFκB, p53, and Bax expression, and higher SOD2 expression than the DM2 group. Immunostaining also demonstrated increased p53 expression in the CA3 region of the hippocampus in the DM groups, indicating neuronal apoptosis, whereas CGA treatment reduced this signal. Conclusions CGA improves memory dysfunction by reducing inflammation, oxidative stress, and neuronal cell death in the hippocampus of diabetic rats.