Effect of Lactobacillus dominance modified by Korean Red Ginseng on the improvement of Alzheimer's disease in mice

Mijung Lee; So-Hee Lee; Min-Soo Kim; Kwang-Sung Ahn; Manho Kim

doi:10.1016/j.jgr.2021.11.001

Effect of Lactobacillus dominance modified by Korean Red Ginseng on the improvement of Alzheimer's disease in mice

J Ginseng Res. 2022 May;46(3):464-472. doi: 10.1016/j.jgr.2021.11.001. Epub 2021 Nov 11.

Authors

Mijung Lee¹, So-Hee Lee¹, Min-Soo Kim², Kwang-Sung Ahn², Manho Kim^{1

3

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Affiliations

¹ Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
² Functional Genome Institute, PDXen. Biosystem Co., Gyeongi-do, Republic of Korea.
³ Neuroscience Dementia Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁴ Protein Metabolism Medical Research Center, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Abstract

Background: Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain.

Methods: Tg2576 were used for the experimental model of AD. They were divided into four groups: wild type (n = 6), AD mice (n = 6), AD mice with 30 mg/kg/day (n = 6) or 100 mg/kg/day (n = 6) of KRG. Following two weeks, changes in gut microbiota were analyzed by Illumina HiSeq4000 platform 16S gene sequencing. Microglial activation were evaluated by quantitative Western blot analyses of Iba-1 protein. Claudin-5, occludin, laminin and CD13 assay were conducted for Blood-brain barrier (BBB) integrity. Amyloid beta (Aβ) accumulation demonstrated through Aβ 42/40 ratio was accessed by ELISA, and cognition were monitored by Novel object location test.

Results: KRG improved the cognitive behavior of mice (30 mg/kg/day p < 0.05; 100 mg/kg/day p < 0.01), and decreased Aβ 42/40 ratio (p < 0.01) indicating reduced Aβ accumulation. Increased Iba-1 (p < 0.001) for reduced microglial activation, and upregulation of Claudin-5 (p < 0.05) for decreased BBB permeability were shown. In particular, diversity of gut microbiota was altered (30 mg/kg/day q-value<0.05), showing increased population of Lactobacillus species. (30 mg/kg/day 411%; 100 mg/kg/day 1040%).

Conclusions: KRG administration showed the Lactobacillus dominance in the gut microbiota. Improvement of AD pathology by KRG can be medicated through gut-brain axis in mice model of AD.

Keywords: AD, (Alzheimer's disease); Alzheimer's disease; Aβ, (Amyloid beta); BBB, (Blood-brain barrier); ELISA, (enzyme-linked immunoassay); Gut-brain axis; KRG, (Korean Red Ginseng); Korean Red Ginseng; Lactobacillus.