Sesamin Promotes Neurite Outgrowth under Insufficient Nerve Growth Factor Condition in PC12 Cells through ERK1/2 Pathway and SIRT1 Modulation.

Sasimol Udomruk,Chayanut Kaewmool,Prachya Kongtawelert,Peraphan Pothacharoen,Thanyaluck Phitak

doi:10.1155/2020/9145458

Sasimol Udomruk, Chayanut Kaewmool + Show 3 more

Open Access

https://doi.org/10.1155/2020/9145458

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Abstract

The promotion of neurogenesis can be a promising strategy to improve and restore neuronal function in neurodegenerative diseases. Nerve growth factor (NGF) plays a key role in neurite outgrowth and synaptic formation during brain repair stage. Nowadays, there are several studies on the developing methods to enhance the endogenous NGF activity for treatment and restore the neuronal function. In this study, the potentiating effect of sesamin, a major lignan in sesame seeds (Sesamum indicum) and oil, on NGF-induced neurogenesis and its involved mechanisms were firstly reported. Sesamin effectively enhanced the PC12 neuron-like cell differentiation and neurite length under insufficient conditions of NGF. The neuronal markers including synaptophysin and growth-associated protein-43 along with the synaptic connections were significantly increased in combination treatment between sesamin and NGF. Moreover, sesamin also increased the level of phospho-ERK1/2 and SIRT1 protein, an important regulatory protein of the neurogenesis process. The neurogenesis was blocked by the specific SIRT1 inhibitor, JGB1741, suggesting that the neuritogenic effect of sesamin was associated with SIRT1 protein modulation. Taken together, the potentiating effect of sesamin on NGF-induced neurogenesis in this finding could be used for alternative treatment in neurodegenerative diseases, including Alzheimer's disease.

Highlights

Neuronal loss and synaptic dysfunction are the main pathological features which linked to cognitive impairments in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [1]
Effect of Sesamin on the Cell Viability of PC12 Cells. e effect of the natural compound on cell viability is crucial to ascertaining the nontoxic concentration. e results showed that sesamin alone, Nerve growth factor (NGF) alone, and the combination treatment had no apparent cytotoxic effect on PC12 cells (Figure 1(a) and 1(b)). us, these conditions were utilized in subsequent experiments
The differentiation of insufficient NGF condition was markedly increased when combined with sesamin treatment in both 24 and 72 h. e potentiation level of combination treatment can be equivalent to an effective dose of NGF at 40 ng/ml (Figures 2(a), 2(b))

Summary

Introduction

Neuronal loss and synaptic dysfunction are the main pathological features which linked to cognitive impairments in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [1]. Developing therapeutic approaches that target on the promotion of neurogenesis is a greatly promising strategy for the neuronal regeneration and reconstruction of synaptic networks in neurodegenerative diseases. Ese effects were involved in the enhancement of the ERK1/2-MAPK signaling pathway and modulation of SIRT1 protein. We demonstrated that sesamin potentiated NGF activity to increase the percentage of neuron-like cell differentiation, neurite length, and synaptic connections in PC12 cells, in vitro model. Taken together, this finding suggests that sesamin might be a potential therapeutic compound for neuronal functions repair in neurodegenerative diseases by promoting neurogenesis

Materials and Methods

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Results