Sun Xiaoxu, Li Shanshan, Xu Lixing, Wang Hao, Ma Zhanqiang, Fu Qiang, Qu Rong, Ma Shiping
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198, China.
Department of Pharmacology of Traditional Chinese Medical Formulae, Nanjing University of Traditional Chinese Medicine, 138, Xianlin Road, Nanjing 210029, China.
Physiol Behav. 2017 May 15;174:162-169. doi: 10.1016/j.physbeh.2017.03.020. Epub 2017 Mar 16.
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.
芍药苷是芍药中的一种天然单萜糖苷，具有多种生物学特性，包括有前景的抗炎活性。目前的证据支持，海马体中的炎症反应、氧化应激以及异常胰岛素信号传导是tau蛋白过度磷酸化的潜在原因，并最终导致认知功能障碍。本研究旨在探讨芍药苷对糖尿病大鼠认知缺陷的影响，并研究其潜在机制，该糖尿病大鼠由高糖、高脂饮食和低剂量链脲佐菌素（STZ）诱导产生。芍药苷治疗通过缩短逃避潜伏期和增加在目标象限的停留时间，有效改善了糖尿病大鼠在莫里斯水迷宫试验中的表现。免疫组织化学染色也显示，给予芍药苷后，海马体中的tau蛋白过度磷酸化得到了预防。该作用与其降低脑内炎性细胞因子（IL-1β和TNF-α）、减少细胞因子信号传导抑制因子2（SOCS2）表达以及促进胰岛素受体底物-1（IRS-1）活性的能力相关。此外，我们还发现给予芍药苷显著促进了蛋白激酶B（Akt）和糖原合酶激酶-3β（GSK-3β）的磷酸化水平。总之，这些结果表明，芍药苷通过调节SOCS2/IRS-1通路对缓解糖尿病相关认知缺陷具有有益作用，并可能为治疗糖尿病相关认知功能障碍提供一种可行的方法。
