Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Food Chem Toxicol. 2020 Mar;137:111160. doi: 10.1016/j.fct.2020.111160. Epub 2020 Jan 25.
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.
7,3',4'-三羟基异黄酮（THIF）是大豆中大量存在的大豆苷元的次生代谢产物。大豆苷元和 7,3',4'-THIF 具有多种药理活性，包括抗氧化和抗变态反应特性。然而，7,3',4'-THIF 对认知功能的影响尚未得到充分研究。在这里，我们使用 Y 迷宫和被动回避测试评估了 7,3',4'-THIF 对记忆的影响。阳性对照组给予多奈哌齐（5mg/kg，po）或吡拉西坦（200mg/kg，ip），实验组给予 7,3',4'-THIF（0.25、0.5 和 1mg/kg，po）。1mg/kg 的 7,3',4'-THIF 和 5mg/kg 的多奈哌齐可有效改善 scopolamine（0.5mg/kg，ip）诱导的小鼠记忆障碍。此外，1mg/kg 的 7,3',4'-THIF 和 200mg/kg 的吡拉西坦可显著增强正常小鼠的记忆。为了在行为实验后检查 7,3',4'-THIF 对认知的潜在机制，在整个海马体中进行了生化测试。1mg/kg 的 7,3',4'-THIF（po）显著恢复了 scopolamine 诱导的胆碱能损伤。此外，脑源性神经营养因子（BDNF）、突触后密度蛋白-95（PSD-95）和突触小体，以及细胞外信号调节激酶 1/2（ERK1/2）和 cAMP 反应元件结合（CREB）的磷酸化，均显著增加了 7,3',4'-THIF（1mg/kg，po）。我们的研究结果表明，7,3',4'-THIF 通过调节胆碱能系统和 BDNF 信号来改善认知功能。
