• Journal of Veterinary Science
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• v.23 no.5
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• pp.74.1-74.16
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• 2022

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

• 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 Ginseng Research
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• v.47 no.1
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

• Journal of Food Hygiene and Safety
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• v.38 no.4
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• pp.273-278
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• 2023

This study aimed to predict the shelf life of black soybean Sunsik to develop a functional labeling system for the product. The Arrhenius equation was used to calculate the shelf life by examining alterations in the dietary fiber and calcium levels of black soybean Sunsik stored at 25, 35, and 50℃ for 0, 6, and 12 months. Dietary fiber and calcium analyses were performed according to the experimental methods specified in the Food Code of the Ministry of Food and Drug Safety. Both black soybean Sunsik (BS) and black soybean Sunsik containing nondigestible maltodextrin and calcium lactate (BSN) exhibited an upward trend in dietary fiber content after 12 months of storage, compared to their initial levels. During storage, the phytate in Sunsik degraded, releasing cations that facilitated the formation of new cross-links between pectic acid and middle lamella, which ultimately increased dietary fiber content. Conversely, the calcium contents of both BS and BSN decreased with prolonged storage. Based on these findings, the expected shelf life of BS and BSN was calculated as 15.65 and 28.34 months, respectively.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.80-80
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• 2002

This study was carried out that to investigate the effects of amino acids supplemented with culture medium on development of porcine embryos cultured in vitro. Cumulus oocyte complexes (COCs) were cultured in the maturation medium containing hormones (0.5$\mu\textrm{g}$/$m\ell$ LH, 0.5$\mu\textrm{g}$/$m\ell$ FSH and 1$\mu\textrm{g}$/$m\ell$ estradiol-17${\beta}$) for 20-22 h at 39$^{\circ}C$ in an atmosphere of 5% CO$_2$in air. Subsequently, COCs were cultured in hormone-free maturation medium for 20-22 h. After maturation for 40-44h, oocytes were removed cumulus cells by pipetting and cultured with epididymal sperm for 5 h in the mTBM. Embryos obtained were divided in 4 groups (1) cultured in NCSU 23 containing 0.4% BSA to blastocyst stage(Control), (2) essential amino acids (EA), (3) non-essential amino acids (NA), (4) mixture of essential and non essential amino acid (EA+NA). All treated groups(2-4) were used a glucose free NCSU 23 medium supplemented with pyruvate (0.33 mM), lactate (4.5 mM) to morula stage. From morula to blastocyst stage embryos of all treated groups were cultured in NCSU 23 containing 0.4% BSA. The rates of cleaved oocytes at 48 h after IVF were from 82% to 88% in the groups of control, EA, NA and EA+NA, respectively. The in vitro developmental rates into blastocysts in the groups of EA and EA+NA were significantly (P<0.05) higher than those of group of control (35.1, 35.4 vs. 19.4%, respectively), however, no significant (P<0.05) between control and NA. In conclusion, supplemented with essential amino acid or mixture of essential and non essential amino acid in the culture medium at morula stage increased the rate of development to blastocyst on in vitro produced porcine embryos.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.75-79
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• 2022

Fresh, washed ginseng can be contaminated with microorganism loads as high as 6.5 log CFU/g for total bacteria and 4.3 log CFU/g for mold. The goal of this study was to test eight antibacterial agents on ginseng. Immersing fresh ginseng washed in 1% (w/w) sodium citrate, sodium diacetate, sodium acetate, citric acid, and sodium lactate solution for 1 h resulted in a bactericidal effect of 31.0-97.5% for total bacteria. Among the organic acids, sodium citrate had the best antibacterial effect, with total bacteria reduced from 6.5 log to 4.9 log CFU/g. A 1% (w/w) vitamin B₁ lauryl sulfate solution with surfactant function by hydrophilic and hydrophobic sites can reduce 2.7 log CFU/g (99.8% inactivation) on total bacteria. In the 1% (w/w) calcium oxide solution, total bacteria were reduced by 3 log, showing an excellent inactivation effect of 99.9%. Calcium oxide is a highly useful material for inactivation of microorganisms in fresh ginseng.

• The Korea Journal of Herbology
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• v.38 no.4
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• pp.21-29
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• 2023

Background : The purpose of this study was to investigate the anti-inflammatory properties of stems and leaves of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (ES) from Gangwon-do. Methods and Results : Stems and leaves of ES were collected from two areas in Gangwon-do: Cheorwon-gun and Samcheok-si. Samples were extracted with water by using the pressurized liquid extraction method and with 70% prethanol A by using the heat reflux extraction method. The anti-inflammatory effects of ES were evaluated through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT), lactate dehydrogenase(LDH) assay, nitric oxide(NO) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). 1) Results showed that ES leaf extractions were not cytotoxic at a concentration of up to 30 ㎍/㎖. The leaves of 70% prethanol A extractions of ES(30 ㎍/㎖) inhibited NO, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) production and decreased the protein level of cyclooxygenase 2(COX-2). There was no significant change in the protein level of inducible nitric oxide synthase(iNOS). The stem extractions of ES did not exhibit anti-inflammatory effects. Conclusions : In this study, the leaves of 70% prethanol A extractions of ES demonstrated anti-inflammatory effect on RAW 264.7 macrophages. The 70% prethanol A extractions have a relatively higher anti-inflammatory effect on RAW 264.7 macrophages than water extractions.

• Journal of the Korean Society of Food Culture
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• v.25 no.6
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• pp.839-846
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• 2010

This study was designed to investigate the effects of Korean Eucommia ulmodies Oliver tea extract on aluminum administered rats. Forty-eight male Sprague-Dawley rats (100${\pm}$10 g) were divided into the following six groups; control group, 3% E. ulmodies tea extract group, 1,000 and 2,000 ppm aluminum ($Al_2(SO_4)_3$ in distilled water) groups, and 1,000 and 2,000 ppm aluminum plus 3% E. ulmodies tea extract groups. The aluminum content in the rat tissues of the aluminum administered group was lower than that in the rat tissue of the aluminum group administered 3% E. ulmodies tea extract. Asparate aminotransferase and alanine aminotransferase levels increased in the aluminum-administered group but were lower in the 3% E. ulmodies tea extract group. Lactate dehydrogenase was lower in the 3% extract E. ulmodies teaaluminum group than that in the aluminum group. Cholinesterase was higher in the 3% E. ulmodies tea-aluminum group than that in the aluminum group. Plasma renin activity levels increased in the aluminum administration group, compared with the aluminum plus 3% E. ulmodies tea group. Plasma aldosterone levels increased in the aluminum administration group compared with the aluminum plus 3% E. ulmodies tea group. These results suggest that an extract of E. ulmodies tea in water has lowering effects on the accumulation of aluminum. It is believed that the E. ulmodies tea had some protective effects in the aluminum-administered rats, but the mechanisms remain obscure.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.17-17
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• 2023

Chrysanthemum zawadskii (C. zawadskii) is used in traditional East Asian medicine for the treatment of various diseases, including inflammatory disease. However, it has remained unclear whether extracts of C. zawadskii inhibit inflammasome activation in macrophages. The present study assessed the inhibitory effect of an ethanol extract of C. zawadskii (CZE) on the activation of the inflammasome in macrophages and the underlying mechanism. Bone marrow[-derived macrophages (BMDMs) were obtained from wild-type C57BL/6 mice. The release of IL-1β and lactate dehydrogenase in response to nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activators, such as ATP, nigericin and monosodium urate (MSU) crystals, was significantly decreased by CZE in lipopolysaccharide(LPS)-primed BMDMs. Western blotting revealed that CZE inhibited ATP-induced caspase-1 cleavage and IL-1β maturation. To investigate whether CZE inhibits the priming step of the NLRP3 inflammasome, we confirmed the role of CZE at the gene level using RT-qPCR. CZE also downregulated the gene expression of NLRP3 and pro-IL-1β as well as NF-κB activation in BMDMs in response to LPS. Apoptosis associated speck-like protein containing a caspase-recruitment domain (CARD) oligomerization and speck formation by NLRP3 inflammasome activators were suppressed by CZE. By contrast, CZE did not affect NLR family CARD domain containing protein 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome activation in response to Salmonella typhimurium and poly(dA:dT) in LPS-primed BMDMs, respectively. The results revealed that three key components of CZE, namely linarin, 3,5-dicaffeoylquinic acid and chlorogenic acid, decreased IL-1β secretion in response to ATP, nigericin and MSU. These findings suggest that CZE effectively inhibited activation of the NLRP3 inflammasome.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.298-309
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• 2024

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.