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

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.

Jiawei Kongsheng Zhenzhong Pill: marker compounds, absorption into the serum (rat), and Q-markers identified by UPLC-Q-TOF-MS/MS

“…The compound 3,6′-disinapoyl sucrose possesses the properties of anti-oxidative stress ( Shi et al, 2015 ; Tang X. et al, 2022 ), counteracting glutamate excitotoxicity ( Hu et al, 2014 ), enhancing neuroplasticity ( Hu et al, 2010 ), and promoting neurogenesis ( Wang et al, 2021 ). Therefore, it was frequently employed to treat conditions such as ischemic stroke, insomnia, amnesia, and depressive disorders.…”

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

“…Tenuigenin promotes the proliferation of neural stem cells and induces their differentiation into neurons and astrocytes ( Chen et al, 2012b ). Both onjisaponin B and tenuifolin enhance the proliferation of neural stem cells, though tenuifolin lacks the capability to facilitate migration and differentiation ( Wang et al, 2021 ), which are crucial for neurogenesis. In contrast, onjisaponin B promotes neural stem cell migration and induces their differentiation into astrocytes ( Wang et al, 2021 ).…”

Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies

“…Crossing the intestinal epithelial barrier and the BBB regulates hippocampal neural differentiation after EGCG interacts with the gut microbiota ( Faria et al., 2011 ; Granja et al., 2019 ). Qisheng Wan formula increased Bacteroidetes abundance in AD mice while reducing NF-κB, IL-6, and TNF-α content ( Xiong et al., 2022 ); one of its active ingredients, Polygala tenuifolia , promotes APP-NSCs proliferation and migration and neuronal differentiation ( Wang X. F. et al., 2021 ), while another ingredient, Acorus tatarinowii Schott , also affects neurogenesis, microglial function and can activate PKA-CREB signaling, enhancing nerve growth factor induced differentiation and neurite length of PC12 cells ( Cai et al., 2016 ; Lam et al., 2016 ). Lipopolysaccharide, amyloids, and other substances produced by Bacteroidetes affect neuroinflammation, possibly by regulating the brain inflammatory microenvironment to regulate neurogenesis ( Zhao and Lukiw, 2018 ), as confirmed by the effects of TCM presented above.…”

“…Traditional Chinese medicine (TCM) is a medical system with a long history and is widely used in the prevention and treatment of nervous system diseases and regulation of body homeostasis. The active ingredients of TCM play an important role in regulating NSCs differentiation, and neuron and glia generation and activation ( Qin et al., 2017 ; Wang X. F. et al., 2021 ). Many reports have indicated that TCM can impact the composition and metabolism of the gut microbiota ( Feng et al., 2019 ).…”