Nutr Res Pract.  2018 Jun;12(3):191-198. 10.4162/nrp.2018.12.3.191.

Comparison of the effect of three licorice varieties on cognitive improvement via an amelioration of neuroinflammation in lipopolysaccharide-induced mice

• Cho MJ
• Kim JH
• Park CH
• Lee AY
• Shin YS
• Lee JH
• Park CG
• Cho EJ

• KMID: 2442292
• DOI: http://doi.org/10.4162/nrp.2018.12.3.191

Abstract

BACKGROUND/OBJECTIVES
Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit.
MATERIALS/METHODS
C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting.
RESULTS
There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B (NFκB) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment.
CONCLUSIONS
The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

Keyword

BDNF; cognitive dysfunction; glycyrrhiza; Glycyrrhiza uralensis; inflammation

MeSH Terms

Alzheimer Disease
Animals
Behavior Rating Scale
Blotting, Western
Brain
Brain-Derived Neurotrophic Factor
Cognition Disorders
Cyclooxygenase 2
Glycyrrhiza uralensis
Glycyrrhiza*
Inflammation
Interleukin-6
Korea
Learning
Memory
Mice*
Neurodegenerative Diseases
Nitric Oxide Synthase Type II
Toll-Like Receptor 4
Water
Brain-Derived Neurotrophic Factor
Cyclooxygenase 2
Interleukin-6
Nitric Oxide Synthase Type II
Toll-Like Receptor 4
Water

Figure

• 

  Fig. 1 Experimental scheduleMice were orally administered with licorice extracts, including G. uralensis, G. glabra, and SW at concentration of 150 mg/kg/day for 7 days. 4 h prior to behavioral testing, mice received LPS injections (2.5 mg/kg/day, i.p., 3 times a week). LPS: Lipopolysaccharide

• 

  Fig. 2 The effects of licorice extracts on spatial memory, measured by the T-maze testData are presented as mean ± SD. * Means the space perception route cognitive abilities for familiar and novel routes are significantly different (P < 0.05) as determined by Student's t-test (n = 6 mice per group). Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

• 

  Fig. 3 The effects of licorice extracts on recognition memory in the novel object recognition testData are presented as mean ± SD. * Means of the space perception route cognitive abilities for familiar and novel routes are significantly different (P < 0.05) as determined by Student's t-test (n = 6 mice per group). Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

• 

  Fig. 4 The effects of licorice extracts on escape latency to the platform in the Morris water maze testData are presented as mean ± SD. a–b Means with different letters are significantly different (P < 0.05) as determined by Duncan's multiple tests (n = 6 mice per group). Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

• 

  Fig. 5 The effects of licorice extracts on escape latency to reach a hidden platform (A) and exposed platform (B) in the Morris water maze testData are presented as mean ± SD. a–b Means with different letters are significantly different (P < 0.05) as determined by Duncan's multiple tests. NS indicates no significant differences among experimental groups (n = 6 mice per group). Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

• 

  Fig. 6 The effects of licorice extracts on inflammation-related protein expressions including TLR4, NF-κB p65, iNOS and COX-2 in LPS-injected mice brainData are presented as mean ± SD. a–e Means with different letters are significantly different (P < 0.05) as determined by Duncan's multiple tests. Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

• 

  Fig. 7 The effects of licorice extracts on IL-6 protein expressions in LPS-injected mice brainData are presented as mean ± SD. a–e Means with different letters are significantly different (P < 0.05) as determined by Duncan's multiple tests. Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

• 

  Fig. 8 The effects of licorice extracts on BDNF protein expressions in LPS-injected mice brainData are presented as mean ± SD. a–e Means with different letters are significantly different (P < 0.05) as determined by Duncan's multiple tests. Normal, 0.9% injection + oral administration of water; Control, LPS injection + oral administration of water; GU, LPS injection + oral administration G. uralensis (150 mg/kg/day); GB, LPS injection + oral administration G. glabra (150 mg/kg/day); SW, LPS injection + oral administration SW (150 mg/kg/day).

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