Banhasasim-Tang Ameliorates Spatial Memory by Suppressing Oxidative Stress through Regulation of ERK/p38 Signaling in Hippocampus of Mice.

Malk Eun Pak,Jong Hyuk Yoon,Min-Gyeong Shin,Yeo Jin Park,Jae Kwang Kim,Younghoon Go,You-Chang Oh,Fabiana Morroni

doi:10.1155/2021/6970578

Abstract

Since ancient times, Banhasasim-tang (BHS) has been used to treat functional dyspepsia in East Asia. Here, we aimed to determine the protective action of BHS on hippocampal neurons against oxidative stress. We investigated the functional effect of BHS on a scopolamine-induced mouse model, and molecular analysis was performed in glutamate-induced HT22 cells. We observed that BHS administration ameliorated memory dysfunction in scopolamine-treated mice. BHS administration also increased neuronal survival and acetylcholine activity and phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus of mice. In hippocampal cells, BHS treatment rescued glutamate-induced cytotoxicity, apoptosis, and oxidative stress. We observed an increase of HO-1 and a decrease of Nrf2 protein expression in glutamate-induced oxidative stress; however, the expression level of these proteins was significantly rescued by BHS treatment. BHS treatment also regulated phosphorylation of p38, p53, ERK, and CREB. Therefore, our data indicated that BHS may reduce oxidative stress through regulation of ERK-CREB and p38-p53 signaling in the hippocampus, resulting in decreased neuronal damage and improved memory in rodent models of neurodegenerative disease.

Highlights

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the gradual dysfunction of memory and cognition, which is in the form of adult-onset dementia [1]
In an in vitro study, we explored if BHS treatment decreased cell apoptosis and reactive oxygen species (ROS) production in hippocampal cells through regulation of extracellular signal-regulated kinase (ERK) and p38 signaling against oxidative stress
We observed that the mice in the SCO group had a significantly increased time and distance to determine the platform compared with those in the CON group

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the gradual dysfunction of memory and cognition, which is in the form of adult-onset dementia [1]. Cholinergic dysfunction, defined by loss of cholinergic markers, occurs in the brain of AD patients and is related to loss of memory [2]. AD is associated with pathogenetic mechanisms such as excitotoxic events and free radical-induced oxidative stress [3, 4]. The pathological characteristics of AD brains include the presence of extensive oxidative stress and neuronal loss [5, 6]. Oxidative stress causes the accumulation of reactive oxygen species (ROS) in neurons, followed by damage to mitochondria and neuronal apoptosis [7]. Removal of ROS or prevention of their formation may delay the onset or slow the progression of AD via reduction of oxidative stress-mediated neuronal toxicity [5]

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