Wang Dongmei, Liu Ling, Li Sanqiang, Wang Chenying
Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luoyang, China.
Department of Pharmacy, Medical College, Henan University of Science and Technology, Luoyang, China.
Physiol Behav. 2018 Jul 1;191:12-20. doi: 10.1016/j.physbeh.2018.03.016. Epub 2018 Mar 20.
Paeoniflorin (PF) is a natural monoterpene glycoside in Paeonia lactiflora pall with anti-diabetic, antioxidant, anti-inflammatory, and neuro-protective properties. This study was designed to investigate the neuroprotective effects of PF against cognitive deficits induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with PF (10 mg/kg per day, intraperitoneally) starting from the first dose of STZ for 21 days showed an improvement in ICV-STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze (MWM) test. PF significantly attenuated STZ induced mitochondrial dysfunction manifested by dramatically elevated cytochrome c oxidase activity and ATP synthesis, and restoration of the mitochondrial membrane potential (MMP), and oxidative stress in hippocampus and in the cortex compared to control. Moreover, PF treatment also markedly increased synaptic density in the CA1 region of the hippocampus compared to control. Furthermore, PF ameliorated defective insulin signaling by up-regulating p-PI3K and p-Akt protein expression while downregulating p-IRS-1 protein expression. Taken together, the outcomes of the current study suggest the therapeutic potential of PF in the cognitive deficits induced by ICV-STZ.
芍药苷（PF）是芍药中的一种天然单萜糖苷，具有抗糖尿病、抗氧化、抗炎和神经保护特性。本研究旨在探讨PF对小鼠脑室内注射链脲佐菌素（STZ）诱导的认知缺陷的神经保护作用。在小鼠中，于第1天和第3天隔天两次脑室内注射STZ（3 mg/kg脑室内注射）。从首次注射STZ开始，每天腹腔注射PF（10 mg/kg/天），持续21天，通过新物体识别和莫里斯水迷宫（MWM）试验评估，结果显示PF改善了ICV-STZ诱导的认知缺陷。与对照组相比，PF显著减轻了STZ诱导的线粒体功能障碍，表现为细胞色素c氧化酶活性和ATP合成显著升高，线粒体膜电位（MMP）恢复，以及海马体和皮质中的氧化应激减轻。此外，与对照组相比，PF处理还显著增加了海马体CA1区的突触密度。此外，PF通过上调p-PI3K和p-Akt蛋白表达同时下调p-IRS-1蛋白表达改善了胰岛素信号缺陷。综上所述，本研究结果表明PF在ICV-STZ诱导的认知缺陷中具有治疗潜力。
