peoniflorin and Cognition-Disorders

Paeoniflorin is a natural monoterpene glycoside in Paeonia lactiflora pall with various biological properties including promising anti-inflammatory activity. Current evidences support that inflammatory reaction, oxidative stress, as well as abnormal insulin signaling in the hippocampus are potential causes of tau hyperphosphorylation and finally induce cognitive dysfunction. The present study aims to explore the effects of paeoniflorin on the cognitive deficits and investigate the underlying mechanisms in diabetic rats induced by a high-sucrose, high-fat diet and low dose of streptozotocin (STZ). Paeoniflorin treatment effectively improved the performance of diabetic rats in the Morris water maze test via decreasing escape latency and increasing the spent time in the target quadrant. Immunohistochemistry staining also had shown that tau hyperphosphorylation in the hippocampus was prevented after paeoniflorin administration. This function was correlated with its abilities of reducing the brain inflammatory cytokines (IL-1β and TNF-α), decreasing suppressor of cytokine signaling 2 (SOCS2) expressions and promoting insulin receptor substrate-1 (IRS-1) activity. Additionally, we also found paeoniflorin administration significantly promoted the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). Together, these results showed that paeoniflorin had beneficial effects on relieving diabetes-associated cognitive deficits via regulating SOCS2/IRS-1 pathway and might provide a feasible method for the treatment of diabetes-associated cognitive dysfunction.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Cognition Disorders; Cytokines; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Hippocampus; Insulin Receptor Substrate Proteins; Male; Maze Learning; Monoterpenes; Phosphorylation; Random Allocation; Rats; Rats, Sprague-Dawley; Signal Transduction; Suppressor of Cytokine Signaling Proteins; tau Proteins

In the present study, the effects of paeoniflorin (PF), a characteristic monoterpene glucoside isolated from Paeoniae Radix, on cerebral infarction, neurological symptoms, tongue protrusion (TP) and performance in the water maze were examined at the chronic stage (4 weeks) of transient cerebral ischemia using a rat middle cerebral artery occlusion (MCAO) model. One-day (10 mg/kg, twice, s.c.) or seven-day (2.5-10 mg/kg, twice a day, s.c.) injection of PF significantly reduced the infarct volume as well as ameliorated the deficits in neurological symptoms caused by transient MCAO at chronic stage. Transient MCAO also induced impairments in TP and performance in the water maze. Treatment with PF was able to reverse or alleviate these impairments. These results indicate that PF may be effective for treatment of stroke.

Topics: Animals; Arterial Occlusive Diseases; Behavior, Animal; Benzoates; Bridged-Ring Compounds; Cognition; Cognition Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Infarction, Middle Cerebral Artery; Male; Maze Learning; Monoterpenes; Neuroprotective Agents; Paeonia; Plant Extracts; Rats; Rats, Sprague-Dawley; Recovery of Function; Swimming