3--4--7-trihydroxyisoflavone and Memory-Disorders

7,3',4'-Trihydroxyisoflavone (THIF) is a secondary metabolite derived from daidzein and is abundantly present in soybeans. Daidzein and 7,3',4'-THIF exhibit several pharmacological activities, including antioxidant and anti-atopic properties. However, the effects of 7,3',4'-THIF on cognitive function have not been fully investigated. Here, we evaluated the effects of 7,3',4'-THIF on memory using Y-maze and passive avoidance tests. The positive control groups were given donepezil (5 mg/kg, p.o.) or piracetam (200 mg/kg, i.p.) and the treated groups were given 7,3',4'-THIF (0.25, 0.5 and 1 mg/kg, p.o.). 7,3',4'-THIF at 1 mg/kg and donepezil at 5 mg/kg effectively ameliorated memory impairments induced by scopolamine (0.5 mg/kg, i.p.) in mice. In addition, 7,3',4'-THIF at 1 mg/kg and piracetam at 200 mg/kg significantly enhanced memory in intact mice. To examine the underlying mechanisms of 7,3',4'-THIF on cognition following behavioral experiments, biochemical tests were performed in the whole hippocampus. 7,3',4'-THIF (1 mg/kg, p.o.) significantly recovered scopolamine-induced cholinergic impairments. Moreover, brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and synaptophysin, along with phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element binding (CREB), were significantly increased by 7,3',4'-THIF (1 mg/kg, p.o.). Our findings indicate that 7,3',4'-THIF improves cognitive function by regulating cholinergic system and BDNF signaling.

Topics: Acetylcholinesterase; Animals; Avoidance Learning; Brain-Derived Neurotrophic Factor; Cyclic AMP Response Element-Binding Protein; Disks Large Homolog 4 Protein; Hippocampus; Isoflavones; Male; Maze Learning; Memory; Memory Disorders; Mice; Mitogen-Activated Protein Kinase Kinases; Nootropic Agents; Phosphorylation; Scopolamine; Signal Transduction; Synaptophysin