• Journal of Ginseng Research
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• v.46 no.1
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• pp.62-70
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• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.166-182
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• 2022

Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei, L. rhamnosus, L. brevis, and L. plantarum, and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 (L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans. Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi, and Listeria monocytogenes. To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo. We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.589-603
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• 2022

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

• Journal of Life Science
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• v.33 no.9
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• pp.693-702
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• 2023

The present study examined the rate of cell growth and differentiation potential into adipocytes in A549 lung adenocarcinoma cells exposed to each adipogenic medium containing glucose metabolism hormones, such as thyroxine (T4) thyroid hormone and glucocorticoid (GC) adrenal steroid hormone, as well as pioglitazone (PGZ), a PPARγ agonist. Following each adipogenic treatment for 2 weeks, the rate of cell growth was significantly (p<0.05) inhibited, and the level of telomerase activity was significantly (p<0.05) decreased in the PGZ-based adipogenic medium containing both T4 and GC hormone compared with those containing each T4 or GC hormone. Moreover, the adiposome-like vesicles were highly reacted with Oil-Red O staining solution, and the levels of transcripts expressed in the differentiating adipocytes for adipogenesis, including adinopectin, leptin, and resistin, were significantly (p<0.05) increased in the PGZ-based adipogenic medium containing both T4 and GC hormone compared with those of the adipogenic medium containing each T4 or GC hormone, implying that adipocytic differentiation has fully occurred in the A549 cancer cells. Based on present observations, the PGZ-based adipogenic medium containing both T4 and GC efficiently induces inhibition of cell growth and cellular differentiation into adipocytes in A549 cancer cells rather than in the adipogenic medium containing only T4 or GC hormone. Adipogenic treatment could provide potential probability in cancer chemotherapy.

• Journal of Life Science
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• v.33 no.6
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• pp.512-522
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• 2023

Cancer with unlimited cell growth is a leading cause of death globally. Various cancer treatments, including surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapy, can be applied alone or in combination depending on the cancer type and stage. New treatments with fewer side effects than previous cancer treatments are continually under development and in demand. Undifferentiated stem cells with unlimited cell growth are gradually changed via cellular differentiation to arrest cell growth. In this study, we reviewed the possibility of treating cancer by using cellular differentiation into the adipocytes in cancer cells. In previous in vitro studies, oral antidiabetic drugs of the thiazolidinedione (TDZ) class, such as rosiglitazone and pioglitazone, were induced into the adipocytes in various cancer cell lines via increased peroxisome proliferator-activated receptor-γ (PPAR γ) expression and glucose uptake, which is the key regulator of adipogenesis and the energy metabolism pathway. The differentiated adipogenic cancer cells treated with TDZ inhibited cell growth and had a less cellulotoxic effect. This adipogenic differentiation treatment suggests a possible chemotherapy option in cancer cells with high and abnormal glucose metabolism levels. However, the effects of the in vivo adipogenic differentiation treatment need to be thoroughly investigated in different types of stem and normal cells with other side effects.

• Journal of Food Hygiene and Safety
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• v.38 no.6
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• pp.442-448
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• 2023

This study aimed to prepare kombucha, a fermented tea beverage, containing Dendropanax morbiferus (DM) leaves and roots, and analyze its antioxidant and intracellular activities. We compared the pH change, total acidity, radical scavenging activity, and oxygen radical absorbance capacity (ORAC) of kombucha fermented with black tea alone and that with added DM leaves or roots during fermentation. Using RAW 264.7, we evaluated the effects of kombucha containing different DM parts on nitric oxide (NO) production and inflammation-related cytokine content in cells. Kombucha containing ethanol extracts of DM leaves (BTK-E-DML) and roots (BTK-E-DMR) showed higher radical scavenging activity and ORAC 3 d after fermentation than that prepared from black tea alone (BTK-Ori). In an in vitro experiment using RAW 264.7, samples were treated with 8 mg/mL kombucha considering cytotoxicity; the lipopolysaccharide (LPS)-induced NO content significantly reduced after BTK-E-DML and BTK-EDMR treatments compared with that after BTK-Ori treatment. Additionally, the levels of interleukin-6 and tumor necrosis factor-alpha, which were LPS-stimulated inflammatory cytokines, significantly decreased in cells treated with BTK-E-DML and BTK-E-DMR 15 d after fermentation compared with those treated with BTK-Ori. In conclusion, these results demonstrate that kombucha fermented with the leaves and roots of DM increases antioxidant activity and can significantly regulate inflammatory responses at the cellular level.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.12a
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• pp.81-81
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• 2020

Pneumonia is infection of air sacs in lungs by bacteria, viruses, fungi and abnormal atmosphere condition. That causes to inflammation and fills up with pus and fulid in air sacs. The symptoms of pneumonia are heavy cough, fever, shortness and rapid respiration and sputum with blood. Also, that remains sequela after the recovery. Thymus quinquecostatus (TQ) has a strong antibacterial effect. That has been used a natural medicine for bronchitis, asthma and nervous inflammation. In this study evaluated anti-inflammatory effects of TQ on IFN (interferon)-γ/TNF (tumor necrosis factor)-α (20 ng/ml) stimulation. MRC-5 cells were seeded at 1 × 10⁵ cells/well in a 24-well plate and stabilized overnight at 37℃. The cells were treated with various concentrations of TQ extracts (DW, 30, 50, 70, 95% EtOH, 0.1~100 mg/ml) for 4h, Subsequently IFN-γ/TNF-α (20 ng/ml) was added to each well and incubated over 12h. the production of inflammatory cytokines were measured by Enzyme-linked immunosorbentassay(ELISA) method. The absorbance was measured at 450 nm using microplate reader. The treatment with TQ extract at dose of 0.1 to 100 mg/ml did not show cytotoxicity in MRC-5 cells (showed cytotoxicity at 95% EtOH 100 mg/ml). The results demonstrated that stimulation of TNF-α/IFN-γ significantly increased the production of inflammatory mediators in the MRC-5 cells compared with unstimulated cells. By contrast, treatment with TQ extreats doses of 0.001 to 10 mM significantly suppressed the production of IL-6 and IL-8. Especially. The higher percent of ethyl alcohol extracts suppressed the production of inflammatory cytokines. This results are considered that essential oil of TQ is extracted according to ethyl alcohol percent. Therefore, TQ has potential to mitigate pulmonary disease that can be used a medicine for pneumonia

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.82-82
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• 2020

염증 (Inflammation)은 물리적인 상처나 세균감염이 되었을 때 손상된 조직을 재생하고 신체를 방어하기 위해 일어나는 선천성 면역반응으로 알려져 있다. 주로 선천면역을 담당하는 대식세포는 lipopolysaccharide, reactive oxygen species와 cytokine 등에 의해 활성화되어 tumor necrosis factor-α. interleukin-1β, interleukin-6 등 염증인자들의 생성에 관여한다. 특히, 산화질소는 superoxide 음이온과 쉽게 반응하고 peroxynitrite와 같은 독성이 강한 산화제를 생성하여 단백질 및 지질의 과산화를 유도하고 세포독성을 일으키는 것으로 보고되고 있다. 따라서 본 연구에서는 항산화 및 항염증 소재를 탐색하기 위해 오미자 (Schisandra chinensis), 꾸지뽕 (Cudrania tricuspidata)을 이용하여 항산화 활성을 평가하고자 하였으며, 세포주를 활용한 세포독성 및 항염증 활성을 확인하고자 하였다. 본 연구는 전북 순창군에서 재배된 오미자, 꾸지뽕을 열 건조(60℃) 통해 건조한 후 분말화하였다. 최적 추출 조건 선정을 위해 다양한 용매 (열수, 증류수, 주정 20, 40, 60%), 온도 (25, 40, 60, 80℃) 및 시간 (1, 2, 3, 4, 5 h) 조건에서 추출된 추출물의 총 폴리페놀 함량을 비교함으로써 최적 조건을 선정하였다. 오미자와 꾸지뽕의 DPPH 및 ABTS radical 소거 활성, 총 플라보노이드 함량을 확인하여 항산화능 및 기능성 성분 함량을 평가하였다. 또한 대식세포주인 Raw 264.7을 활용하여 MTT assay, 산화질소 생성 억제 활성을 확인하여 세포독성 및 항염증 활성을 평가하였다. 실험 결과, 오미자 및 꾸지뽕은 각각 주정 40%, 60℃ 그리고 증류수, 60℃에서 추출 시 가장 높은 총 폴리페놀 함량 (약 98.3 mg GAE/g 및 88.2 mg GAE/g)을 함유하며, DPPH 라디칼 소거 활성은 약 44.6% 및 24.4%, ABTS 라디칼 소거 활성은 약 30.3% 및 40.8%로 확인되었다. 총 플라보노이드 함량은 약 21.80 mg QE/g 및 35.68 mg QE/g으로 확인되었다. 또한 오미자 및 꾸지뽕 기능성 추출물을 100 ug/mL 처리 시 세포 독성이 나타나지 않는 것으로 확인되었으며, NO 생성량을 약 56.3% 및 21.7% 저감시켜 항염증 효능을 나타내는 것으로 확인되었다.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.