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. 2018 Feb 18:2018:3479083.
doi: 10.1155/2018/3479083. eCollection 2018.

Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

Yu Ri Kim  1 , Min Young Kwon  2 , Malk Eun Pak  3   4 , So Hyun Park  2 , Jin Ung Baek  2 , Byung Tae Choi  1   2   3   4
Affiliations

Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

Yu Ri Kim et al. Evid Based Complement Alternat Med. .

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.

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Figures

Figure 1
Figure 1
Schematic diagram of the overall experiment and behavioral testing. WMT, Morris water maze test; PAT, passive avoidance test.
Figure 2
Figure 2
Effect of Gagam-Palmultang on memory-related behaviors. (a) Morris water maze test. (b) Passive avoidance test. Treatment with Gagam-Palmultang improves spatial learning and memory impairments caused by scopolamine. Data are presented as mean ± SEM. +P < 0.05, ++P < 0.01, and +++P < 0.001 versus basal; ##P < 0.01 and ###P < 0.001 versus control; ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 versus vehicle.
Figure 3
Figure 3
Effect of Gagam-Palmultang on ACh and AChE activity in the hippocampus. (a) ACh level. (b) AChE activity. The activity of AChE is significantly decreased by treatment with Gagam-Palmultang. Data are presented as mean ± SEM. #P < 0.05 versus control; ∗P < 0.05 versus vehicle.
Figure 4
Figure 4
Effect of Gagam-Palmultang on AChE expression in the hippocampus. (a) Western blot and its histogram. (b) Photomicrograph for AchE/DAPI staining and its histogram. Compared to vehicle-treated mice, S + PH mice tend to show significantly decreased AChE expression. ##P < 0.01 versus control; ∗P < 0.05 and ∗∗P < 0.01 versus vehicle. Scale bar: 200 μm.
Figure 5
Figure 5
Effect of Gagam-Palmultang on the protein level of PI3K, Akt, and ERK in the hippocampus. (a) Western blot for PI3K and Akt and its histogram. (b) Western blot for ERK and its histogram. Protein levels of pPI3K and pERK are significantly increased by treatment with Gagam-Palmultang. Data are expressed as mean ± SEM. &P < 0.05 and &&P < 0.01 versus PH; ∗P < 0.05 and ∗∗∗P < 0.001 versus vehicle.
Figure 6
Figure 6
Effect of Gagam-Palmultang on the expression of pPI3K and ERK in the hippocampus. (a) Photomicrograph for pPI3K/DAPI staining and its histogram. (b) Photomicrograph for pERK/DAPI staining and its histogram. Expression of pPI3K and pERK is significantly increased by treatment with Gagam-Palmultang. Data are expressed as mean ± SEM. #P < 0.05 versus control; ∗P < 0.05 and ∗∗P < 0.01 versus vehicle; &P < 0.05 versus S + PH. Scale bar: 200 μm.
Figure 7
Figure 7
Effect of Gagam-Palmultang on the protein levels of CREB and mBDNF in the hippocampus. (a) Western blot for CREB and its histogram. (b) Western blot for mBDNF and its histogram. Protein levels of pCREB are significantly increased by treatment with Gagam-Palmultang. Data are expressed as mean ± SEM. #P < 0.05 versus control; ∗P < 0.05 versus vehicle.
Figure 8
Figure 8
Effect of Gagam-Palmultang on the expression of pCREB and mBDNF in the hippocampus. (a) Photomicrograph for pCREB/DAPI staining and its histogram. (b) Photomicrograph for mBDNF/DAPI staining and its histogram. Expression of pCREB is significantly increased by treatment with Gagam-Palmultang. Data are expressed as mean ± SEM. #P < 0.05 versus control; ∗∗P < 0.01 and ∗∗∗P < 0.001 versus vehicle; &&P < 0.01 versus S + PH. Scale bar: 200 μm.
Figure 9
Figure 9
Effect of Gagam-Palmultang on the cell proliferation in the hippocampus. Photomicrograph for Ki67 or Ki67/NeuN staining and its histogram. The numbers of Ki67+/NeuN+ cells in the hippocampus tend to increase after treatment with Gagam-Palmultang. ∗P < 0.05 versus vehicle. Scale bar: 200 μm.
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