• BMB Reports
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• v.55 no.6
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• pp.275-280
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• 2022

The treatment of atopic dermatitis (AD) is challenging due to its complex etiology. From epidermal disruption to chronic inflammation, various cells and inflammatory pathways contribute to the progression of AD. As with immunosuppressants, general inhibition of inflammatory pathways can be effective, but this approach is not suitable for long-term treatment due to its side effects. This study aimed to identify a plant extract (PE) with anti-inflammatory effects on multiple cell types involved in AD development and provide relevant mechanistic evidence. Degranulation was measured in RBL-2H3 cells to screen 30 PEs native to South Korea. To investigate the anti-inflammatory effects of Parasenecio auriculatus var. matsumurana Nakai extract (PAE) in AD, production of cytokines and nitric oxide, activation status of FcεRI and TLR4 signaling, cell-cell junction, and cell viability were evaluated using qRT-PCR, western blotting, confocal microscopy, Griess system, and an MTT assay in RBL-2H3, HEK293, RAW264.7, and HaCaT cells. For in vivo experiments, a DNCBinduced AD mouse model was constructed, and hematoxylin and eosin, periodic acid-Schiff, toluidine blue, and F4/80-staining were performed. The chemical constituents of PAE were analyzed by HPLC-MS. By measuring the anti-degranulation effects of 30 PEs in RBL-2H3 cells, we found that Paeonia lactiflora Pall., PA, and Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. show an inhibitory activity of more than 50%. Of these, PAE most dramatically and consistently suppressed cytokine expression, including IL-4, IL-9, IL-13, and TNF-α. PAE potently inhibited FcεRI signaling, which mechanistically supports its basophil-stabilizing effects, and PAE downregulated cytokines and NO production in macrophages via perturbation of toll-like receptor signaling. Moreover, PAE suppressed cytokine production in keratinocytes and upregulated the expression of tight junction molecules ZO-1 and occludin. In a DNCB-induced AD mouse model, the topical application of PAE significantly improved atopic index scores, immune cell infiltration, cytokine expression, abnormal activation of signaling molecules in FcεRI and TLR signaling, and damaged skin structure compared with dexamethasone. The anti-inflammatory effect of PAE was mainly due to integerrimine. Our findings suggest that PAE could potently inhibit multi-inflammatory cells involved in AD development, synergistically block the propagation of inflammatory responses, and thus alleviate AD symptoms.

• Journal of Life Science
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• v.32 no.9
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• pp.712-720
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• 2022

The purpose of this study was to investigate the efficacy of rat corneal-derived epithelial cells as an in vitro model to evaluate the harmfulness of the cornea caused by particulate matter 2.5 (PM_2.5). To establish an experimental model for the effect of PM_2.5 on corneal epithelial cells, it was confirmed that primary cultured cells isolated from rat eyes were corneal epithelial cells through pan-cytokeratin staining. Our results showed that PM_2.5 treatment reduced cell viability of primary rat corneal epithelial (RCE) cells, which was associated with the induction of apoptosis. PM_2.5 treatment also increased the generation of reactive oxygen species due to mitochondrial dysfunction. In addition, the production of nitric oxide and inflammatory cytokines was increased in PM_2.5-treated RCE cells. Furthermore, through heatmap analysis showing various expression profiling between PM_2.5-exposed and unexposed RCE cells, we proposed five genes, including BLNK, IL-1RA, Itga2b, ABCb1a and Ptgs2, as potential targets for clinical treatment of PM-related ocular diseases. These findings indicate that the primary RCE cell line is a useful in vitro model system for the study of PM_2.5-mediated pathological mechanisms and that PM2.5-induced oxidative and inflammatory responses are key factors in PM2.5-induced ocular surface disorders.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.40 no.4
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• pp.504-511
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• 1995

This study was conducted to investigate the superoxide dismutase (SOD) characteristics and antioxidant activity by nonenzymatic(Fe$^{2+}$/Ascorbate) and Fe$^{3+}$-ADP/NADPH method in perilla(Perilla frutescens var. japonica Hara.) and jaso(Perilla frutescens Briton var. acuta Kudo.) leaves. The characteristics were evaluated by the nitro blue tetrazolium reduction method. Perilla leaves contained three or four major SODs depending on the varieties. The inhibitor test indicated that the Perilla leaves contained two Cu /ZnSODs and one or two FeSODs, but Jaso leaves have only Cu/ZnSOD. However, no varietal differences were detected in the Cu /ZnSOD isozyme patterns. FeSODs, however, showed different varietal isozyme patterns through the different combinations of the two FeSOD isozymes. Among MeOH extractes, "mil yang 2" showed very strong antioxidant activity. Relatively large differences in the levels of SOD and antioxidant activity detected in the Perilla varietites. There was significantly different in the comparison between perilla leaves and red jaso leaves.s.etween perilla leaves and red jaso leaves.

• Molecules and Cells
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• v.45 no.12
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• pp.886-895
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• 2022

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

• Korean Journal of Environmental Biology
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• v.41 no.1
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• pp.41-53
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• 2023

E171, a mixture of titanium dioxide, has been widely used as a food additive due to its whitening effect and low toxicity. However, it has been proven that E171 is no longer safe for public health. So far, there are insufficient studies on the toxic effects of E171 on organisms especially using standardized test methods. In this study, toxicity assessments of E171 to two aquatic species, water flea (Daphnia magna) and zebrafish (Danio rerio), were performed using modified standardized test methods based on the physicochemical properties of E171. The hydrodynamic diameter, polydispersity index, and turbiscan stability index (TSI) were measured to ensure the dispersion stability of E171 in exposure media during the test period. The EC₅₀ for immobilization of water flea was 141.7 mg L^-1 while zebrafish was not affected until 100 mg L^-1 of E171. Measurements of reactive oxygen species (ROS) and antioxidant enzyme activities confirmed that E171 induced oxidative stress, leading to the activation of superoxide dismutase and catalase in both water flea and zebrafish, although the expression of antioxidant enzyme genes differed between species. These results suggested the potential risk of E171 to aquatic organisms and provided toxicological insights into the impacts of E171 on the environment.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.28-37
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• 2022

Pregnancy requires an important interpretation of thyroid function tests. The presence of anti-thyroid antibodies and viral infectious agents affect the health of both the fetus and the mother. Hence, a selective evaluation of thyroid function in pregnancy is required. This study is a retrospective cross-sectional survey to examine the correlation between thyroid hormones and viral infections during pregnancy. The results showed that the triiodothyronine (T3) decreased with increasing age, especially in the hepatitis C virus (HCV)-positive group (P<0.01). In addition, although negative for the human immunodeficiency virus (HIV), thyroxine (FT4) showed a significant increase in near-threshold or twin pregnant women (P<0.05). The thyroid stimulating hormone (TSH) was highly distributed at the age of 30, and there was no statistically significant correlation with other viral infection factors. In addition, as a result of dividing and analyzing the result of TSH by the quantiles, FT4 and T3 showed a positive correlation but showed a negative correlation with TSH (P<0.05). Therefore, the evaluation of prenatal thyroid screening during pregnancy and viral infection factors should reflect the time of pregnancy, exposure to infection, and the quantitative values. Adequate thyroid hormone and viral infections availability is important for an uncomplicated pregnancy and optimal fetal development.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• Clean Technology
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• v.29 no.2
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• pp.109-117
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• 2023

The purpose of this study is to develop a method for separating antioxidants and sugars from grape skin extract. The extract was first mixed with a variety of organic solvents to investigate whether the separation was feasible. When employing acetone, ethanol, dimethylsulfoxide, or dimethylformamide, the organic solvent-extract combination formed a single phase. However, when benzene, ethyl acetate, or n-hexane was added to the extract, the mixture separated into an organic and an aqueous phase and the pigments remained in the aqueous phase. On the other hand, when polyethylene glycol-2,000 (PEG-2000) and sodium citrate were added to the extract, the mixture was separated into three layers, with the majority of the flavonoids migrating to the top layer and 53% of the extract's glucose migrating to the bottom layer. The top layer had significant antioxidant activity, whereas the bottom layer showed no antioxidant activity. The glucose recovery in the bottom layer increased as the molecular weight of PEG increased and the highest recovery (67%) was observed when PEG-8,000 was added. The highest flavonoid separation was observed with PEG-2,000, followed by PEG-8,000 and PEG-400. The flavonoid separation when PEG-2,000 was added resulted in a flavonoid recovery of 48% and 0.2% from the top and bottom layers, respectively. Examining the effect of the separated solution using the agar disc diffusion method on yeast cell growth confirmed that the addition of the extract, the top, and the bottom layer did not inhibit cell growth.

• Journal of Korean Medicine for Obesity Research
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• v.23 no.1
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• pp.1-9
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• 2023

Objectives: Noni fruit juice (NFJ) is liquor extracted from Morinda citrifolia (noni) fruit and has been used as an herbal remedy in many countries. However, the NFJ's anti-adipogenic and anti-inflammatory effects on adipocytes are poorly understood. The purpose of this study was to explore the commercially standardized NFJ effects on lipid accumulation throughout 3T3-L1 preadipocytes differentiation and interleukin-1β (IL-1β)-mediated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 preadipocytes. Methods: Cellular lipid accumulation and triglyceride (TG) content in differentiating 3T3-L1 preadipocytes were assessed subsequently via the Oil Red O staining and AdipoRed assay. MTS assay was used to examine NFJ cytotoxicity in (differentiating) 3T3-L1 preadipocytes. Immunoblotting and reverse transcriptase polymerase chain reaction analysis were used to measure the expression levels of target protein and mRNA in (differentiating) 3T3-L1 preadipocytes, respectively. Results: NFJ treatment at 150 μL/mL led to a substantial reduction of fat accumulation and TG content during 3T3-L1 adipogenesis with no discernable impact on the cell viability. Of note, while NFJ treatment (150 μL/mL) largely inhibited the CCAAT/enhancer-binding protein-α (C/EBP-α) and peroxisome proliferator-activated receptor-β (PPAR-β) protein expressions, it did not influence PPAR-γ in differentiating 3T3-L1 preadipocytes. Of interest, treatment with IL-1β at 20 ng/mL for 4 hours elicited in firm induction of iNOS mRNA expression in 3T3-L1 preadipocytes. However, NFJ treatment at 100 or 200 μL/mL greatly attenuated the IL-1β-induced iNOS mRNA expression in 3T3-L1 preadipocytes. Conclusions: NFJ has anti-adipogenic and anti-inflammatory effects on (differentiating) 3T3-L1 preadipocytes which are in part intervened via control of the expression of C/EBP-α, PPAR-β, and iNOS.