Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus

Kim, Sang Hyun; Jeon, Seong Gak; Kim, Kyoung Ah; Kim, Jwa Jin; Song, Eun Ji; Jeon, Yukyoung; Kim, Eunbin; Lee, Kyung Bok; Kwak, Jong Hwan; Moon, Minho

doi:10.3390/nu9070794

Cited by 18 publications

(15 citation statements)

References 60 publications

(91 reference statements)

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“…Secondly, LDIR up-regulates the expression of synaptophysin and intercellular adhesion molecules (CAM) [ 84 , 85 ], which enable synaptic plasticity and promote synaptogenesis. Enhancement of synaptogenesis can improve cognitive function [ 86 ]. Thirdly, LDIR up-regulates heat shock protein 70, a protein that has been reported to regulate misfolded protein aggregation and may reduce the toxicity of Aβ [ 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

Kim

Chung

Ngoc

et al. 2020

IJMS

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Alzheimer’s disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aβ deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aβ pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aβ deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aβ accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aβ-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aβ deposition and memory loss.

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Section: Discussionmentioning

confidence: 99%

Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

Kim

Chung

Ngoc

et al. 2020

IJMS

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“…Platycodon grandiflorum (PG) has been used as an oriental herbal medicine native to East Asia (Korea, China, and Japan). It has various beneficial effects such as anti-inflammatory [12] and antibacterial [13] activities, improvement of liver function [14], and enhancement of cognitive ability [15]. In particular, platycodin D and platycodin D3 as main active ingredients of PG have anti-inflammatory activities, as it was shown to mitigate the inflammatory response induced by lipopolysaccharides (LPS) in RAW 264.7 (a macrophage cell line) cells [16].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of fermented Platycodon grandiflorum extract through NF-κB signaling in RAW 264.7 cells

Park

Lee

2020

Nutr Res Pract

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BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dosedependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides-and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immuneenhancing agent acting via AMPK-NF-κB signaling pathway.

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“…Surprisingly, it has been reported that administration of PGE for 1 month increases the number of DCX-positive cells in 12-month-old healthy mice [ 49 ]. Although conflicting results exist regarding the effects of PGE on AHN [ 30 , 49 ], it is speculated that different treatment doses, total number, duration of administration, age of animals, and extraction methods displayed different effects. Since adult neurogenesis depends on age and AD progression [ 50 ], it is necessary to validate the effect of PGE on adult neurogenesis according to age and AD progression.…”

Section: Discussionmentioning

confidence: 99%

“…Mice were classified as WT and 5XFAD through genotyping of tail DNA (APP forward: 5-AGG ACT GAC CAC TCG ACC AG-3, APP reverse: 5-CGG GGG TCT AGT TCT GCA T-3, PSEN1 forward: 5-AAT AGA GAA CGG CAG GAG CA-3, PSEN1 reverse: 5-GCC ATG AGG GCA CTA ATC AT-3) ( Table S2 ). The PGE was dissolved in saline before oral injection and administered to 6-month-old female WT and 5XFAD mice for 3 weeks at a dose of 100 mg/kg daily [ 30 ]. The behavioral experiments were repeated twice to improve statistical precision.…”

Section: Methodsmentioning

confidence: 99%

“…In the experimental environment, the temperature and humidity were maintained at 23 ± 1 °C and 60 ± 10%, respectively. The three arms of the Y-maze (each 8 cm wide× 30 cm long × 15 cm tall) are located at an angle of 120° [ 30 ]. To measure the memory function, mice were first allowed to adapt themselves to the experimental environment for a week before the behavioral experiment.…”

Section: Methodsmentioning

confidence: 99%

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Platycodon grandiflorum Root Protects against Aβ-Induced Cognitive Dysfunction and Pathology in Female Models of Alzheimer’s Disease

et al. 2021

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Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by irreversible cognitive dysfunction. Amyloid beta (Aβ) peptide is an important pathological factor that triggers the progression of AD through accumulation and aggregation, which leads to AD-related pathologies that consequently affect cognitive functions. Interestingly, several studies have reported that Platycodon grandiflorum root extract (PGE), besides exhibiting other bioactive effects, displays neuroprotective, anti-neuroinflammatory, and cognitive-enhancing effects. However, to date, it is not clear whether PGE can affect AD-related cognitive dysfunction and pathogenesis. Therefore, to investigate whether PGE influences cognitive impairment in an animal model of AD, we conducted a Y-maze test using a 5XFAD mouse model. Oral administration of PGE for 3 weeks at a daily dose of 100 mg/kg significantly ameliorated cognitive impairment in 5XFAD mice. Moreover, to elucidate the neurohistological mechanisms underlying the PGE-mediated alleviative effect on cognitive dysfunction, we performed histological analysis of hippocampal formation in these mice. Histopathological analysis showed that PGE significantly alleviated AD-related pathologies such as Aβ accumulation, neurodegeneration, oxidative stress, and neuroinflammation. In addition, we observed a neuroprotective and antioxidant effect of PGE in mouse hippocampal neurons. Our findings suggest that administration of PGE might act as one of the therapeutic agents for AD by decreasing Aβ related pathology and ameliorating Aβ induced cognitive impairment.

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Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus

Cited by 18 publications

References 60 publications

Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease

Immunomodulatory effects of fermented Platycodon grandiflorum extract through NF-κB signaling in RAW 264.7 cells

Platycodon grandiflorum Root Protects against Aβ-Induced Cognitive Dysfunction and Pathology in Female Models of Alzheimer’s Disease

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