• Korean Journal of Plant Resources
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• v.36 no.4
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• pp.257-263
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• 2023

Autophagy contributes to enhancing the immune system (innate and adaptive immune system) against foreign pathogens. Autophagy of macrophages is used as a major indicator for developing vaccine adjuvants to increase the adaptive immune response. In this study, water extracts from Rosa acicularis leaves (RAL) increased the production of immunostimulatory mediators and phagocytic activity in RAW264.7 cells. RAL increased p62/SQSTM1 expression. Inhibition of TLR4, JNK, and PI3K/AKT blocked RAL-mediated increase of p62/SQSTM1. RAL activated JNK and PI3K/AKT signaling. RAL-mediated activations of JNK and PI3K/AKT signaling were reversed by TLR4 inhibition. Taken together, it is believed that RAL-mediated autophagy may be dependent on activating via TLR4-dependent activation of JNK and PI3K/AKT signaling in macrophages.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• The Korean Journal of Food And Nutrition
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• v.37 no.1
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• pp.17-29
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• 2024

To increase industrial applicability of Astragalus membranaceus (AM) as immunostimulating materials, hot-water extract (AME) was prepared from AM and fermented with Kimchi-lactic acid bacteria (Lactobacillus sakei & Leuconostoc mesenteroides) to prepare fermented AM-postbiotics (FAME). Although FAME prepared from AM-postbiotics did not show a significant enhancement in macrophage stimulating activity compared to non-fermented AME, crude polysaccharide (FAME-CP) fractionated by EtOH precipitation from FAME showed significantly higher macrophage stimulating activity than AME-CP. Compared to AME-CP, FAME-CP showed dramatic changes in component sugar and molecular weight distribution. FAME-CP was a polysaccharide with a major molecular weight distribution of 113.4 kDa containing Man (44.2%), Glc (19.3%), Gal (10.2%), GalA (10.2%), and Ara (7.4%) as sugar components. FAME-CP with enhanced macrophage stimulatory activity not only increased expression levels of mRNA genes encoding macrophage-activated factors (iNOS, TNF-α, MCP-1, IL-6, and COX-2), but also led the nuclear translocation of activated p65 and c-Jun. In conclusion, crude polysaccharide from AM-postbiotics fermented with lactic acid bacteria could increase industrial applicability as a functional material with enhanced immunostimulating activity than AME-CP.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.303-312
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• 2024

Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone-treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.672-680
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• 2023

Background: Korean Red Ginseng (KRG), the steamed root of Panax ginseng, has pharmacological activities for immunological and neurodegenerative disorders. But, the role of KRGE in multiple sclerosis (MS) remains unclear. Purpose: To determine whether KRG extract (KRGE) could inhibit demyelination in corpus callosum (CC) of cuprizone (CPZ)-induced murine model of MS Methods: Male adult mice were fed with a standard chow diet or a chow diet supplemented with 0.2% (w/w) CPZ ad libitum for six weeks to induce demyelination while were simultaneously administered with distilled water (DW) alone or KRGE-DW (0.004%, 0.02 and 0.1% of KRGE) by drinking. Results: Administration with KRGE-DW alleviated demyelination and oligodendrocyte degeneration associated with inhibition of infiltration and activation of resident microglia and monocyte-derived macrophages as well as downregulation of proinflammatory mediators in the CC of CPZ-fed mice. KRGE-DW also attenuated the level of infiltration of Th1 and Th17) cells, in line with inhibited Mrna expression of IFN-γ and IL-17, respectively, in the CC. These positive effects of KRGE-DW mitigated behavioral dysfunction based on elevated plus maze and the rotarod tests. Conclusion: The results strongly suggest that KRGE-DW may inhibit CPZ-induced demyelination due to its oligodendroglial protective and anti-inflammatory activities by inhibiting infiltration/activation of immune cells. Thus, KRGE might have potential in therapeutic intervention for MS.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.644-653
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• 2024

Considering the emergence of various infectious diseases, including the coronavirus disease 2019 (COVID-19), people's attention has shifted towards immune health. Consequently, immune-enhancing functional foods have been increasingly consumed. Hence, developing new immune-enhancing functional food products is needed. Pinus densiflora pollen can be collected from the male red pine tree, which is commonly found in Korea. P. densiflora pollen extract (PDE), obtained by water extraction, contained polyphenols (216.29 ± 0.22 mg GAE/100 g) and flavonoids (35.14 ± 0.04 mg CE/100 g). PDE significantly increased the production of nitric oxide (NO) and reactive oxygen species (ROS) but, did not exhibit cytotoxicity in RAW 264.7 cells. Western blot results indicated that PDE induced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. PDE also significantly increased the mRNA and protein levels of cytokines and the phosphorylation of IKKα/β and p65, as well as the activation and degradation of IκBα. Additionally, western blot analysis of cytosolic and nuclear fractions and immunofluorescence assay confirmed that the translocation of p65 to the nucleus after PDE treatment. These results confirmed that PDE increases the production of cytokines, NO, and ROS by activating NF-κB. Therefore, PDE is a promising nutraceutical candidate for immune-enhancing functional foods.

• Nutrition Research and Practice
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• v.18 no.4
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• pp.464-478
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• 2024

BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.

• The Korea Journal of Herbology
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• v.39 no.4
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• pp.1-9
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• 2024

Objective : In this study, the anti-obesity effect of Fragaria orientalis (FO) on high-fat diet-induced obese mice was investigated. Drug treatment methods are widely used as obesity treatment methods, but research using various natural products is being conducted due to safety concerns. This study aims to evaluate the anti-obesity effect of FO extract, a natural product derived from Mongolia. Methods : C57BL/6 mice were used and divided into three groups, normal diet group, high-fat diet group, and high-fat diet with FO oral treatment group at a dose of 300 mg/kg. Extract was orally provided everyday for 6 weeks. Body Weight and food intake were measured every 2 days and blood lipid profiles and liver function in the sacrificed mice were evaluated. In addition, protein expression in hepatic tissue and histomorphological changes in liver and adipose tissue were observed. Results : Body weight, adipose tissue weight and FER were significantly lower in a high-fat diet with FO treatment than fed only high-fat diet. There was a significant difference between the high-fat diet and the FO-treated high-fat diet mice. As a result of analyzing lipid metabolism-related genes in hepatic tissue, all of p-AMPK, p-ACC, PPAR-α, CPT-1, and UCP-1 showed significant increases, and PPAR-γ also decreased significantly compared to the high-fat diet group. Conclusion : Overall, these results indicate that FO is effectual in improving obesity, suggesting that it can be used as a possible material for anti-obesity agents or functional supplements for weight control.

• Journal of Ginseng Research
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• v.48 no.5
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• pp.481-493
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• 2024

Background: Post-weaning social isolation (SI) reduces sociability, gene expressions including myelin genes in the medial prefrontal cortex (mPFC), and alters microbiome compositions in rodent models. Korean Red Ginseng (KRG) and its major ginsenoside Rb1 have been reported to affect myelin formation and gut metabolites. However, their effects under post-weaning SI have not been investigated. This study investigated the effects of KRG and Rb1 on sociability, gene expressions in the mPFC, and gut metabolites under post-weaning SI. Methods: C57BL/6J mice were administered with water or KRG (150, 400 mg/kg) or Rb1 (0.1 mg/kg) under SI or regular environment (RE) for 2 weeks during the post-weaning period (P21-P35). After this period, mice underwent a sociability test, and then brains and ceca were collected for qPCR/immunohistochemistry and nontargeted metabolomics, respectively. Results: SI reduced sociability compared to RE; however, KRG (400 mg/kg) and Rb1 significantly restored sociability under SI. In the mPFC, expressions of genes related to myelin, neurotransmitter, and oxidative stress were significantly reduced in mice under SI compared to RE conditions. Under SI, KRG and Rb1 recovered the altered expressions of several genes in the mPFC. In gut metabolomics, 313 metabolites were identified as significant among 3027 detected metabolites. Among the significantly changed metabolites in SI, some were recovered by KRG or Rb1, including metabolites related to stress axis, inflammation, and DNA damage. Conclusion: Altered sociability, gene expression levels in the mPFC, and gut metabolites induced by two weeks of post-weaning SI were at least partially recovered by KRG and Rb1.

• Anatomy and Cell Biology
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• v.55 no.3
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• pp.320-329
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• 2022

Aluminium exposure has been linked with developmental neurotoxicity in humans and experimental animals. The study aimed to evaluate the ameliorative effect of Tamarindus indica on the developing cerebellar cortex, neurobehavior, and immunohistochemistry of the cerebellar cortex following prenatal aluminum chloride (AlCl₃) exposure. Pregnant timed Wistar rats were divided into 5 groups (n=4). Group I (negative control) was given distilled water, group II was treated with 200 mg/kg of AlCl₃, group III were given 200 mg/kg of AlCl₃ and 400 mg/kg of ethyl acetate leaf fraction of Tamarindus indica (EATI), group IV were given 200 mg/kg of AlCl₃ and 800 mg/kg of EATI, and group V were treated with 200 mg/kg of AlCl₃ s/c and 300 mg/kg of vitamin E for 14 days (prenatal day 7-21) via the oral route. Male pups (n=6) were randomly selected and taken for neurobehavioral studies, and humanely sacrificed via intraperitoneal injection of thiopental sodium. The cerebellum was removed, fixed and tissue processed for histological and immunohistochemical studies. The results revealed that prenatal AlCl₃ exposure impacted neurodevelopment and neurobehaviour among exposed pups. Prenatal AlCl₃ exposure was marked with delayed cytoarchitectural development of the cerebellar cortex and increased GFAP expression in the cerebellar cortex. On the other hand, treatment with EATI and vitamin E were marked with significant improvements. The present study therefore concluded treatment with EATI shows an ameliorative effect to prenatal AlCl₃ exposure.