Center for Neuromedicine of Dalian Municipal Central Hospital, 42 Xuegong Street, Shahekou District, Dalian, Liaoning Province, 116033, People's Republic of China.
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD Port, Dalian, Liaoning Province, 116600, People's Republic of China.
BMC Complement Med Ther. 2021 Oct 25;21(1):267. doi: 10.1186/s12906-021-03437-5.
Alzheimer's disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6'-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis.
NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively.
DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice.
Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.
阿尔茨海默病（AD）是全球最常见的痴呆症，目前仍没有令人满意的药物或治疗策略。远志是一种具有多种神经保护作用的传统中药。本研究旨在探讨远志的三种活性成分[3,6′-二咖啡酰基蔗糖（DISS）、远志皂苷 B（OB）和远志酮（TEN）]对神经干细胞（NSCs）增殖和分化的影响，以鉴定促进海马神经发生的潜在活性成分。
从新生 C57BL/6 小鼠海马中分离 NSCs，并转染突变型淀粉样前体蛋白（APP）基因，建立 AD 细胞模型（APP-NSCs）。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和乳酸脱氢酶（LDH）检测，神经球形成试验、5-溴-2'-脱氧尿苷（BrdU）掺入试验和免疫荧光（IF）染色分析评估 NSCs 的增殖和分化。APP/PS1 转基因小鼠给予潜在活性成分 DISS 治疗 4 周。采用 Morris 水迷宫（MWM）、尼氏染色和 IF 染色试验分别评估认知功能、神经损伤和海马神经发生。
DISS 增强 APP-NSCs 增殖和神经元分化的能力最强，其次是 OB 和 TEN。此外，DISS 治疗 4 周可显著改善成年 APP/PS1 转基因小鼠的认知障碍、神经元损伤和神经发生障碍。
我们的研究结果表明，DISS 是 PT 中触发 AD 小鼠模型海马神经发生增加最有效的成分。
