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

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12906-021-03437-5.

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Most cited references 58

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Mechanisms and functional implications of adult neurogenesis.

Chunmei Zhao, Wei Deng, Fred Gage (2008)

The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry. We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease.

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Morris water maze: procedures for assessing spatial and related forms of learning and memory.

Charles V. Vorhees, Michael Williams (2006)

The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.

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Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease

Elena P. Moreno-Jiménez, Miguel Flor-García, Julia Terreros-Roncal … (2019)

The hippocampus is one of the most affected areas in Alzheimer's disease (AD)1. Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life2. This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry3,4. Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential. By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced. These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.

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Author and article information

Contributors

Jing-xian Yang: jingxianyang63@126.com

Xiao-le Hu: 280617642@qq.com

Journal

Journal ID (nlm-ta): BMC Complement Med Ther

Journal ID (iso-abbrev): BMC Complement Med Ther

Title: BMC Complementary Medicine and Therapies

Publisher: BioMed Central (London )

ISSN (Electronic): 2662-7671

Publication date (Electronic): 25 October 2021

Publication date PMC-release: 25 October 2021

Publication date Collection: 2021

Volume: 21

Electronic Location Identifier: 267

Affiliations

[1 ]GRID grid.452337.4, ISNI 0000 0004 0644 5246, Center for Neuromedicine of Dalian Municipal Central Hospital, , 42 Xuegong Street, Shahekou District, ; Dalian, Liaoning Province 116033 People’s Republic of China

[2 ]GRID grid.411464.2, ISNI 0000 0001 0009 6522, School of Pharmacy, , Liaoning University of Traditional Chinese Medicine, ; 77 Life One Road, DD Port, Dalian, Liaoning Province 116600 People’s Republic of China

Article

Publisher ID: 3437

DOI: 10.1186/s12906-021-03437-5

PMC ID: 8543956

PubMed ID: 34696749

SO-VID: 6a590c01-0844-4bf6-9d41-bd60fc3529ee

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 5 July 2021

Date accepted : 6 October 2021

Custom metadata

Keywords: alzheimer disease,neurogenesis,neural stem cells,polygala tenuifolia,3,6′-disinapoyl sucrose

Data availability:

Keywords: alzheimer disease, neurogenesis, neural stem cells, polygala tenuifolia, 3,6′-disinapoyl sucrose

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

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Alternative approaches to Alzheimer's Disease

Most cited references 58

Mechanisms and functional implications of adult neurogenesis.

Morris water maze: procedures for assessing spatial and related forms of learning and memory.

Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease

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