Paeonol Ameliorates Cognitive Deficits in Streptozotocin Murine Model of Sporadic Alzheimer’s Disease via Attenuation of Oxidative Stress, Inflammation, and Mitochondrial Dysfunction

Intracerebroventricular (ICV) microinjection of diabetogenic drug streptozotocin (STZ) in rodents consistently produces a model of sporadic Alzheimer's disease (sAD) which is characterized by tau pathology and concomitant cognitive decline, insulin resistance, neuroinflammation, oxidative stress, and mitochondrial malfunction. Paeonol is an active phenolic component in some medicinal plants like Cortex Moutan with neuroprotective efficacy via exerting anti-inflammatory and anti-oxidative effects. This study was conducted to assess beneficial effect of paeonol in amelioration of cognitive deficits in ICV STZ rat model of sAD. STZ (3 mg/kg) was microinjected into the lateral ventricles on days 0 and 2, and paeonol was given p.o. at two doses of 25 (low) or 100 (high) mg/kg from day 0 (post-surgery) till day 24 post-STZ. Cognitive performance was evaluated in different tasks, and oxidative stress- and inflammation-related parameters were measured in addition to immunohistochemical assessment of glial fibrillary acidic protein (GFAP) as a marker of astrocytes. Paeonol at the higher dose ameliorated cognitive deficits in Barnes maze, novel object recognition (NOR) task, Y maze, and passive avoidance test. In addition, paeonol partially reversed hippocampal malondialdehyde (MDA), reactive oxygen species (ROS), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase, glutathione reductase, tumor necrosis factor α (TNFα), interleukin 6 (IL-6), mitochondrial membrane potential (MMP), myeloperoxidase (MPO), and acetylcholinesterase (AChE) activity. Paeonol treatment was also associated with lower hippocampal immunoreactivity for GFAP. This study showed that paeonol can alleviate cognitive disturbances in ICV STZ rat model of sAD via ameliorating neuroinflammation, oxidative stress, mitochondrial dysfunction, and also through its attenuation of astrogliosis.