PI3K/Akt signaling pathway is involved in the neurotrophic effect of senegenin

Pi, Ting; Zhou, Xiao‐Qiu; Cai, Liang; Zhang, Wei; Su, Chao-Fen; Wu, Wu-tian; Ren, Xiao‐Ming; Luo, Hongyu

doi:10.3892/mmr.2015.4652

Cited by 14 publications

(8 citation statements)

References 29 publications

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“…Notably, Sen could increasing the phosphorylation of PI3K and Akt, which was consistent with the previous study. 64 Therefore, Sen may reduce apoptosis by regulating the expression of Bcl-2 family proteins.…”

Section: Discussionmentioning

confidence: 99%

Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway

Ren¹,

Zhang²,

Zhao³

et al. 2022

NDT

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Background/Aim Apoptosis and oxidative stress have been considered as key events in the pathogenesis of Alzheimer’s disease (AD). Senegenin (Sen), the major and most effective ingredient of Radix Polygalae , which has anti-apoptotic and anti-oxidative effects. The aim of this study was to investigate the anti-apoptotic and anti-oxidant effects of Sen on Aβ 1-42 -induced PC12 cells apoptosis and oxidative stress as well as its possible signaling pathway. Methods Rat pheochromocytoma (PC12) cells were treated by 20 μM Aβ 1-42 and then divided into 5 different treatment groups (Control; Aβ 1-42 20 μM; Aβ 1-42 20 μM + Sen 10 μM; Aβ 1-42 20 μM + Sen 30 μM; Aβ 1-42 20μM + Sen 60 μM). PC12 cells activity was detected by MTT assay. Colony formation assay was performed to assess the clonogenic ability of cells. The cell apoptosis was detected by Annexin-V/PI staining. The pro-apoptotic protein (Bax), anti-apoptotic protein (Bcl-2), anti-oxidative stress factor (HO-1, Nuclear Nrf2, Total Nrf2) and pathway-related protein (Akt, P-Akt, PI3K, P-PI3K) were tested by Western blot. The reactive oxygen species (ROS) level was assessed with a DCFH-DA probe. Results The results indicated that Sen dose-dependently increased cell viability and reduced the number of apoptotic cells. The ratio of P-PI3K/PI3K and P-Akt/Akt increased in a dose-dependent manner under the treatment of Sen, suggesting that Sen might activate the PI3K/Akt signaling pathway. Moreover, Sen upregulates the ratio of Bcl-2/Bax. Further study revealed that Sen can play an antioxidant role in enhancing HO-1, promoting Nrf2 nuclear translocation and reducing ROS accumulation to reduce oxidative stress. Conclusion Sen is effective in inhibiting apoptosis and oxidative stress in Aβ 1-42 -induced PC12 cells, which likely contribute to the development of novel therapies for AD.

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Section: Discussionmentioning

confidence: 99%

Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway

Ren¹,

Zhang²,

Zhao³

et al. 2022

NDT

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“…The studies showed that the effects may be related to stimulating different upstream pathways of CREB via the MAPK/ERK1/2, phosphoinositide-3 kinase (PI3K), and CREB-BDNF pathways, which was demonstrated in vitro (19). The neurotrophic effects of senegenin were significantly inhibited by the A 2A receptor antagonist ZM241385 and the specific PI3K inhibitor LY294002, suggesting that senegenin may be involved in the PI3K/Akt signaling pathway (50,59).…”

Section: Neuroprotective Mechanisms Neuronal Synaptic Plasticity and Proliferationmentioning

confidence: 98%

“…DISS and tenuifoliside (A, B, and C), two natural oligosaccharide esters from P. tenuifolia roots, improved neuronal synaptic plasticity, promoted nerve cell proliferation, and showed neuroprotective effects via inhibiting glucocorticoid-induced NOS hyper-activation, upregulating the phosphorylation of CREB, and increasing the expression of BDNF in corticosterone-induced SH-SY5Y cells (19). Senegenin was also found to promote neurite outgrowth and neuronal survival in primary cultured rat cortical neurons (50,59). The studies showed that the effects may be related to stimulating different upstream pathways of CREB via the MAPK/ERK1/2, phosphoinositide-3 kinase (PI3K), and CREB-BDNF pathways, which was demonstrated in vitro (19).…”

Section: Neuroprotective Mechanisms Neuronal Synaptic Plasticity and Proliferationmentioning

confidence: 99%

Protective Effects and Mechanism of Radix Polygalae Against Neurological Diseases as Well as Effective Substance

et al. 2021

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Radix Polygalae (also known as Yuanzhi in China) is the dried rhizome of Polygala tenuifolia Willd. or Polygala sibirica L., which is a famous Chinese herb and has been widely used for centuries in traditional medicines including expectorants, tonics, tranquilizers, antipsychotic, and so on. This article reviews the neuroprotective effects of Radix Polygalae in preclinical models of central nervous system (CNS) disorders, especially anxiety, depression, declining cognition, Alzheimer's disease (AD), and Parkinson's disease (PD). The chemical composition of Radix Polygalae as well as the underlying mechanisms of action were also reviewed. We found that Radix Polygalae possesses a broad range of beneficial effects on the abovementioned conditions. The multifold mechanisms of action include several properties such as antioxidant and associated apoptotic effects; anti-inflammatory and associated apoptotic effects; neurogenesis, regeneration, differentiation, and neuronal plasticity improvement; hypothalamic–pituitary–adrenal axis (HPA) regulation; neurotransmitter release; and receptor activation (A2AR, NMDA-R, and GluR). Nevertheless, the detailed mechanisms underlying this array of pharmacological effects observed in vitro and in vivo still need further investigation to attain a coherent neuroprotective profile.

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“…At a dose of 5 lg/mL, senegenin promoted neuritogenesis with a notable increase in the number of neurites, mean length, and maximum length by up-regulating MAP2 and Gap-43 expression or inhibition of ASK1 and JNK signalling pathways (Jesky and Chen 2016). Another research suggests that senegenin exerts neuroprotective effects may be associated with the PI3K/Akt signalling pathway (Pi et al 2016). In addition, P. tenuifolia extract can also promote the nerve growth factor release in astroglial cells (Yabe et al 2003).…”

Section: Promote Neuronal Proliferationmentioning

confidence: 99%

Polygala tenuifolia: a source for anti-Alzheimer’s disease drugs

Deng

Zhao

Liu

et al. 2020

Pharmaceutical Biology

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Context: Alzheimer's disease (AD) is a chronic neurodegenerative disease that originates from central nervous system lesions or recessions. Current estimates suggest that this disease affects over 35 million people worldwide. However, lacking effective drugs is the biggest handicap in treating AD. In traditional Chinese medicine (TCM), Polygala tenuifolia Willd. (Polygalaceae) is generally used to treat insomnia, memory dysfunction and neurasthenia. Objective: This review article explores the role of P. tenuifolia and its active components in anti-Alzheimer's disease. Methods: Literature for the last ten years was obtained through a search on PubMed, SciFinder, CNKI, Google Scholar, Web of Science, Science Direct and China Knowledge Resource Integrated with the following keywords: Polygala tenuifolia, polygalasaponin XXXII (PGS 32), tenuifolin, polygalacic acid, senegenin, tenuigenin, Alzheimer's disease. Results: Polygala tenuifolia and its active components have multiplex neuroprotective potential associated with AD, such as anti-Ab aggregation, anti-Tau protein, anti-inflammation, antioxidant, anti-neuronal apoptosis, enhancing central cholinergic system and promote neuronal proliferation. Conclusions: Polygala tenuifolia and its active components exhibit multiple neuroprotective effects. Hence, P. tenuifolia is a potential drug against Alzheimer's disease, especially in terms of prevention.

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PI3K/Akt signaling pathway is involved in the neurotrophic effect of senegenin

Cited by 14 publications

References 29 publications

Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway

Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway

Protective Effects and Mechanism of Radix Polygalae Against Neurological Diseases as Well as Effective Substance

Polygala tenuifolia: a source for anti-Alzheimer’s disease drugs

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