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. 2019 Dec 30;12(1):97.
doi: 10.3390/nu12010097.

Evaluating the Memory Enhancing Effects of Angelica gigas in Mouse Models of Mild Cognitive Impairments

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Free PMC article

Evaluating the Memory Enhancing Effects of Angelica gigas in Mouse Models of Mild Cognitive Impairments

Minsang Kim et al. Nutrients. .
Free PMC article

Abstract

(1) Background: By 2050, it is estimated that 130 million people will be diagnosed with dementia, and currently approved medicines only slow the progression. So preventive intervention is important to treat dementia. Mild cognitive impairment is a condition characterized by some deterioration in cognitive function and increased risk of progressing to dementia. Therefore, the treatment of mild cognitive impairment (MCI) is a possible way to prevent dementia. Angelica gigas reduces neuroinflammation, improves circulation, and inhibits cholinesterase, which can be effective in the prevention of Alzheimer's disease and vascular dementia and the progression of mild cognitive impairment. (2) Methods: Angelica gigas (AG) extract 1 mg/kg was administered to mildly cognitive impaired mice, models based on mild traumatic brain injury and chronic mild stress. Then, spatial, working, and object recognition and fear memory were measured. (3) Result: Angelica gigas improved spatial learning, working memory, and suppressed fear memory in the mild traumatic brain injury model. It also improved spatial learning and suppressed cued fear memory in the chronic mild stress model animals. (4) Conclusions: Angelica gigas can improve cognitive symptoms in mild cognitive impairment model mice.

Keywords: Angelica gigas; chronic mild stress; mild cognitive impairment; traumatic brain injury.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Spatial learning by Angelica gigas (AG) in traumatic brain injury (TBI) and chronic mild stress (CMS) mice as measured by the latency to the platform in the Morris water maze (MWM). (A) TBI model. There were repetitive training (within) effects [F(4,104) = 13.9, p < 0.001] and treatment group (between) effects [F(3,26) = 2.27, p = 0.044], but with non-significant within–between interaction differences [F(12,104) = 1.1, p = 0.36]. The post-hoc pairwise comparison showed a difference between control vs. TBI (p = 0.033), TBI vs. TBI + AG (p = 0.041). (B) CMS model. There were repetitive training effects [F(4,196) = 31.3, p < 0.001], treatment group effects [F(3,49) = 3.1, p = 0.034], and within–between interactions [F(12,196) = 2.2, p = 0.012]. Post-hoc pairwise comparison revealed a difference between the control and CMS groups (p = 0.019), AG vs. CMS (p = 0.01), CMS vs. CMS + AG (p = 0.042). All data were normally distributed and are represented as means ± S.E.M. Control: vehicle (DW) treated; AG: Angelica gigas 1 mg/kg; TBI: vehicle treated + traumatic brain injury; TBI + AG: Angelica gigas 1 mg/kg + traumatic brain injury; CMS: vehicle treated + chronic mild stress; CMS + AG: Angelica gigas 1 mg/kg + chronic mild stress. Repeated measure ANOVA, Tukey’s HSD post-hoc test.
Figure 2
Figure 2
Short-term working memory by AG in TBI and CMS mice, measured by the percent alternation in the Y-maze. (A) TBI model. There were before–after (within) effects [F(1,28) = 3.57, p = 0.012], treatment group (between) effects [F(3,28) = 3.23, p = 0.081], and within–between interactions [F(3,28) = 3.28, p = 0.036]. There were no before–after changes in the control (p = 0.6) and TBI (p = 0.38), but improvements in the AG (p = 0.008) and TBI + AG (p = 0.047). (B) CMS model. There were before–after effects [F(1,36) = 6.2, p = 0.018] and treatment group effects [F(3,36) = 11.8, p < 0.001], but no significant within–between interaction differences [F(3,36) = 1.5, p = 0.24]. There was no before–after change in the control group (p = 031), AG (p = 0.97) or CMS (p = 0.33) groups. However, there was an increase of % alternation in the CMS + AG group (p = 0.006). All data were normally distributed and are represented as means ± S.E.M. Control: vehicle (DW) treated; AG: Angelica gigas 1 mg/kg; TBI: vehicle treated + traumatic brain injury; TBI+AG: Angelica gigas 1 mg/kg + traumatic brain injury; CMS: vehicle treated + chronic mild stress; CMS+AG: Angelica gigas 1 mg/kg + chronic mild stress. Repeated measures ANOVA, Tukey’s HSD post-hoc test.
Figure 3
Figure 3
Object recognition memory by AG in the TBI and CMS mice as measured by the recognition time index in the novel object test. (A) TBI model. There were before–after (within) effects [F(1,28) = 8.3, p = 0.008], treatment group (between) effects [F(3,28) = 0.67, p = 0.58], and within–between interaction effects [F(3,28) = 3.6, p = 0.026]. There was no before–after change in the control (p = 0.93), AG (p = 0.59) and TBI + AG (p = 0.97) groups, but there were decreases in the TBI (p = 0.001) group. (B) CMS model. There were no before-after effects [F(1,36) = 0.32, p = 0.57], treatment group effects [F(3,36) = 1.2, p = 0.31], or within–between interactions [F(3,36) = 0.12, p = 0.95]. All data were normally distributed and are represented as means ± S.E.M. Control: vehicle (DW) treated; AG: Angelica gigas 1 mg/kg; TBI: vehicle treated + traumatic brain injury; TBI + AG: Angelica gigas 1 mg/kg + traumatic brain injury; CMS: vehicle treated + chronic mild stress; CMS+AG: Angelica gigas 1 mg/kg + chronic mild stress. Repeated measures ANOVA, Tukey’s HSD post-hoc test.
Figure 4
Figure 4
Fear memory by AG in TBI and CMS mice, as measured by the freezing time in the fear conditioning test. (A) Fear acquisition in the TBI model. There were time (within) effects [F(5,140) = 45.7, p < 0.001], treatment group (between) effects [F(3,28) = 3.25, p = 0.03], but no within–between interaction differences [F(15,140) = 1.1, p = 0.36]. There were no differences between the treatment groups at base, cue1, cue2, cue3, or cue4. However, the differences between the TBI and TBI + AG groups were significant (p = 0.039). In addition, the differences between the TBI and control groups (p = 0.16), and TBI vs. AG (p = 0.13) groups were not significant. (B) Consolidated contextual fear memory in TBI model. There were no group differences in the freezing response to the context [F(3,28) = 0.36, p = 0.78). (C) Consolidated cued fear in the TBI model. There were procedure (within) effects [F(1, 28) = 61.6, p < 0.001], no treatment group (between) effects [F(3,28) = 0.29, p = 0.83], or within–between interactions [F(3,28) = 0.64, p = 0.59]. There was a significant increase in the freezing comparing cue vs. precue in the control (p < 0.001), AG (p < 0.001), TBI (p = 0.005), and TBI + AG groups (p < 0.001). (D) Fear acquisition in the CMS model. There were time (within) effects [F(5,95) = 27.8, p < 0.001], treatment group (between) effects [F(3,19) = 4.9, p = 0.011], but no within–between interaction effects [F(15,95) = 0.47, p = 0.95]. Fear acquisition in AG (p = 0.021), CMS (p = 0.035), and CMS + AG (p = 0.001) were lower than controls throughout the fear acquisition procedure. There were no statistical differences among the AG, CMS, and CMS + AG groups. (E) Consolidated contextual fear memory in the CMS model. There were group differences in the freezing response to the context [F(3,19) = 9.8, p < 0.001). The contextual fear in AG (p = 0.002), CMS (p = 0.008), and CMS + AG (p < 0.001) was lower than those of the controls. (F) Consolidated cued fear in the CMS model. There were procedure (within) effects [F(1,19) = 54.7, p < 0.001], treatment group (between) effects [F(3,19) = 9.3, p = 0.001], and within–between interaction differences [F(3,19) = 4.8, p = 0.012]. There was a significant increase in freezing between cue and precue in the control (p < 0.001), CMS (p < 0.001), and CMS + AG (p = 0.002) groups, but not in the AG group (p = 0.31). At pre-cue, the control vs. CMS + AG (p = 0.001) groups were statistically different. At cue, the control vs. AG, (p = 0.004); control vs. CMS + AG, (p < 0.001); CMS vs. CMS + AG, (p = 0.017) were all statistically different. All data were normally distributed and are represented as means ± S.E.M. Control: vehicle (DW) treated; AG: Angelica gigas 1 mg/kg; TBI: vehicle treated + traumatic brain injury; TBI + AG: Angelica gigas 1 mg/kg + traumatic brain injury; CMS: vehicle treated + chronic mild stress; CMS + AG: Angelica gigas 1 mg/kg + chronic mild stress. ** p < 0.01, *** p < 0.001 vs. control. # p < 0.05 vs. CMS. ANOVA and repeated measures ANOVA, Tukey’s HSD post-hoc test.
Figure 5
Figure 5
Experimental outline of mild cognitive impairment mice models induced by TBI (Cohort 1) and CMS (Cohort 2). TBI: Traumatic brain injury, CCI: Controlled cortical impact, Y-maze: Y shaped maze test, NOT: Novel object test, MWM: Morris water maze, FC: Fear conditioning, CMS: Chronic mild stress.

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