Abstract

From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and mature brain-derived neurotrophic factor (mBDNF) expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments.

Highlights

  • Aging-related cognitive- and memory-deficit conditions, such as Alzheimer’s disease (AD), are becoming a public health problem as the lifespan of humans is increasing in the modern industrial society [1, 2]

  • We evaluated the beneficial effects of GagamPalmultang on scopolamine-induced memory impairment in mice

  • In the passive avoidance test for valuating short-term memory, vehicle mice exhibited a shorter entry latency than control mice; scopolamine-administered mice treated with GagamPalmultang, or with piracetam, exhibited a slightly longer latency, but there were no significant differences in the entry latency [Figure 2(b)]

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Summary

Introduction

Aging-related cognitive- and memory-deficit conditions, such as Alzheimer’s disease (AD), are becoming a public health problem as the lifespan of humans is increasing in the modern industrial society [1, 2]. The central cholinergic system is important in cognitive function and deficits in this system are linked to conditions such as aging-induced dementia, AD, and other neurodegenerative diseases [3,4,5]. Brain-derived neurotrophic factor (BDNF) is strongly linked to mechanisms underlying consolidation of recognition memory, and modulation of this neurotrophic factor affects cognitive function [9,10,11]. BDNF stimulates intracellular signaling cascades implicated in the molecular mechanisms of learning and memory enhancement [11]. Activation of downstream signaling pathways by BDNF, including the phosphatidylinositide-3-kinase (PI3K)/protein kinase B (Akt) and extracellular-signal-related kinase (ERK)/mitogenactivated protein kinase (MAPK) pathways that are known

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