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

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.

Phosphodiesterase 7 inhibitor reduces stress-induced behavioral and cytoarchitectural changes in C57BL/6J mice by activating the BDNF/TrkB pathway

“…CREB phosphorylation plays a regulatory role in neuronal growth, survival, and synaptic connectivity, further impacting the function of the hippocampus ( Lonze and Ginty, 2002 ). Specifically, CREB can control the synthesis of specific proteins, including brain-derived neurotrophic factor (BDNF), an important biological molecule for maintaining the normal function of neurons ( Pak et al, 2021 ; Lu et al, 2022 ). Further, previous studies found that BDNF plays an important regulatory role in neuron growth and differentiation by specifically binding to its receptor, tyrosine kinase receptor B (TrkB) in the hippocampus, meanwhile, the hormone level changes resulting from severe stress exposure have a regulatory effect on the BDNF/TrkB signaling pathway ( Notaras and van den Buuse, 2020 ; Camuso et al, 2022 ).…”