Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice

• Published in: BMC complementary and alternative medicine 2021-10, Vol.21 (1), p.267-267, Article 267
• Main Authors: Wang, Xiao-Feng, Xiao, Hong-He, Wu, Yu-Tong, Kong, Liang, Chen, Ji-Cong, Yang, Jing-Xian, Hu, Xiao-le
• Format: Article
• Language: English
• Subjects: 3,6′-disinapoyl sucrose; adults; Advertising executives; Alzheimer disease; Alzheimer Disease - drug therapy; Alzheimer's disease; amyloid; Amyloid beta-protein; Amyloid precursor protein; Animal cognition; Animals; Apoptosis; Assaying; Biotechnology; Brain; Cell differentiation; Cell proliferation; Chinese medicine; cognition; Cognitive ability; complement; Constituents; dementia; Dementia disorders; Differentiation; Disease Models, Animal; drugs; Epidermal growth factor; Experiments; fluorescent antibody technique; genes; Genetic engineering; genetically modified organisms; Herbal medicine; Hippocampus; Hippocampus - drug effects; Immunofluorescence; L-Lactate dehydrogenase; Laboratory animals; Lactate dehydrogenase; Lactic acid; Medical research; Medicine, Chinese; Medicine, Chinese Traditional - methods; Medicine, Experimental; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Structure; Morris Water Maze Test; mutants; neonates; Neural stem cells; Neural Stem Cells - drug effects; Neurodegenerative diseases; Neurogenesis; Neurogenesis - drug effects; Neurons; Neuroprotection; Oriental traditional medicine; Penicillin; Polygala - chemistry; Polygala tenuifolia; Presenilin 1; Proteins; Software; Staining; Stem cell transplantation; Stem cells; Sucrose; therapeutics; Traditional Chinese medicine; Transgenic animals; Transgenic mice
• ISSN: 2662-7671; 2662-7671; 1472-6882
• 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.