School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; Suzhou Psychiatric Hospital, Suzhou 215008, China.
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Phytomedicine. 2016 May 15;23(5):460-7. doi: 10.1016/j.phymed.2016.02.014. Epub 2016 Mar 3.
Compounds that possess a pyrrolidone skeleton are a rich resource for the discovery of nootropic drugs. Oleracein E (OE), which possesses both tetrahydroisoquinoline and pyrrolidone skeletons, was first isolated from the medicinal plant Portulaca oleracea L. and was thought to be an active component in the cognition-improvement effect induced by this herb. The aim of this study was to investigate the effect of OE on cognitive impairment in senescent mice and its underlying mechanism of action.
Senescent Kunming mice were established by the intraperitoneal injection of D-galactose (D-gal, 1250 mg/kg/d) and NaNO2 (90 mg/kg/d) for 8 weeks. OE (3 mg/kg/d, 15 mg/kg/d) was orally administered for 8 weeks, and the nootropic drug piracetam (PA, 400 mg/kg/d) was used as a positive control. A Morris water maze was used to assess cognitive ability. GSH and MDA levels and T-AOC, SOD, and CAT activities in the brain or plasma were determined. Hippocampal morphology was observed by HE staining, and expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic proteins Bax and Caspase-3 was observed by immunohistochemical staining.
Large-dosage treatments with D-gal/NaNO2 for 8 weeks significantly reduced survival, impaired spatial memory capacity, compensatorily up-regulated GSH level and T-AOC and SOD activities, decreased CAT activity, and induced hippocampal neuronal damage and apoptosis as reflected by the apparent low expression of Bcl-2 and high expression of Bax and Caspase-3. OE significantly prolonged lifespan and was more potent than PA. Similar to PA, OE at 15 mg/kg/d improved memory capacity. The underlying mechanism of action was related to the reversal of abnormal brain antioxidant biomarkers (GSH, T-AOC, and SOD) to normal levels and the inhibition of hippocampal neuronal apoptosis.
OE from P. oleracea is an active compound for improving cognitive function and is also a candidate nootropic drug for the treatment of age-related dementia.
具有吡咯烷酮骨架的化合物是发现益智药物的丰富资源。Oleracein E（OE），其同时具有四氢异喹啉和吡咯烷酮骨架，最初从药用植物马齿苋（Portulaca oleracea L.）中分离出来，被认为是该草药诱导认知改善作用的活性成分。本研究旨在探讨 OE 对衰老小鼠认知障碍的影响及其作用机制。
采用腹腔注射 D-半乳糖（D-gal，1250mg/kg/d）和亚硝酸钠（90mg/kg/d）8 周建立衰老昆明小鼠模型。OE（3mg/kg/d，15mg/kg/d）灌胃给药 8 周，益智药吡拉西坦（PA，400mg/kg/d）作为阳性对照。采用 Morris 水迷宫评估认知能力。测定脑或血浆中 GSH 和 MDA 水平以及 T-AOC、SOD 和 CAT 活性。HE 染色观察海马形态学变化，免疫组化染色观察抗凋亡蛋白 Bcl-2 和促凋亡蛋白 Bax、Caspase-3 的表达。
8 周大剂量 D-gal/NaNO2 处理显著降低了存活率，损害了空间记忆能力，代偿性地上调了 GSH 水平和 T-AOC、SOD 活性，降低了 CAT 活性，并诱导了海马神经元损伤和凋亡，表现为 Bcl-2 表达明显降低，Bax 和 Caspase-3 表达明显升高。OE 显著延长了寿命，其效果强于 PA。与 PA 相似，15mg/kg/d 的 OE 改善了记忆能力。其作用机制与将异常的脑抗氧化生物标志物（GSH、T-AOC 和 SOD）恢复正常水平以及抑制海马神经元凋亡有关。
马齿苋中的 OE 是一种改善认知功能的活性化合物，也是治疗与年龄相关的痴呆症的候选益智药物。
