Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.
Department of Integrative Medicine, School of TCM, Xinjiang Medical University, Urumqi, China.
Brain Behav. 2020 May;10(5):e01602. doi: 10.1002/brb3.1602. Epub 2020 Mar 15.
Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear.
Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC-MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step-down passive-avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T-SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining.
After one-half or 1 month of intragastric administration, GAPT can ameliorate scopolamine-induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine-treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB.
GAPT can improve the learning and memory ability of scopolamine-induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury.
胆碱能功能障碍和氧化应激是阿尔茨海默病（AD）的关键机制。益智方（GAPT），又称益智合剂（GEPT，由人参、淫羊藿、远志和莪术等几种草药的有效成分组成）或金思维，是一种已获专利的中药复方，临床上广泛用于改善学习记忆障碍，但它是否通过保护胆碱能神经元和减少氧化应激损伤发挥神经保护作用尚不清楚。
雄性 ICR 小鼠腹腔注射东莨菪碱（3mg/kg）建立学习记忆障碍模型。采用 LC-MS 法研究益智方的化学成分和体内代谢物。东莨菪碱注射后，进行跳台被动回避试验（SDPA）和 Y 迷宫试验评估学习能力和认知功能。此外，采用 ELISA 检测乙酰胆碱酯酶（AChE）、乙酰胆碱（ACh）、胆碱乙酰转移酶（ChAT）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GPX）和总超氧化物歧化酶（T-SOD）的酶活性。Western blot 观察 AChE、ChAT、SOD1 和 GPX1 的蛋白表达，免疫组化染色观察 ChAT、SOD1 和 GPX1 的分布。
益智方半剂量或 1 个月灌胃给药可改善东莨菪碱致学习记忆障碍小鼠的行为变化。还可降低 MDA 活性和 AChE 蛋白表达水平，增加 Ach 活性，提高东莨菪碱处理小鼠的 ChAT、SOD 和 GPX 活性和蛋白表达水平。益智方连续灌胃 1.5 个月后，松果菊苷、丹酚酸 A、人参皂苷 Rb1、人参皂苷 Rg2、土木香酸、β-细辛醚可被吸收进入小鼠血液并通过血脑屏障。
益智方可改善东莨菪碱致小鼠的学习记忆能力，其机制可能与保护胆碱能神经元和减少氧化应激损伤有关。
