• Microbiology and Biotechnology Letters
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• v.47 no.2
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• pp.195-200
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• 2019

The purpose of this study was to investigate the melanogenesis inhibiting activity of the ethanol extract from Polygonum amphibium L. Firstly, the n-hexane (Hx), chloroform ($CHCl_3$), ethyl acetate (EA), n-butanol (BuOH), and water (Water) fractions were isolated from the P. amphibium L. ethanol extract. The efficacy of melanogenesis was found to significantly decrease via the EA and BuOH fractions when compared to the control in B16F10 cells. EA particularly showed the lowest melanin content in B16F10 cells when compared to all the other extracts. Concentration-dependent inhibition of melanin synthesis was also observed in the EA fraction at concentrations below $50{\mu}g/ml$, which did not exhibit cytotoxicity in B16F10 cells. Notably, the expression of three key proteins (tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2), which are involved in melanogenesis, were significantly decreased via the EA fraction. EA also inhibited body pigmentation in vivo in a zebrafish model. Overall, we demonstrated melanogenesis suppression using the EA fraction from P. amphibium L., which could be a potential candidate for an antimelanogenesis agent.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.933-941
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• 2021

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

• Advances in nano research
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• v.12 no.6
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.11
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• pp.1744-1752
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• 2013

We investigated the protective effect of UVB inducing photodamage from mulberry extract (ME) and Lithospermum erythrorhizon extract (LE). The contents of total anthocyanin and shikonin as a color compound of ME and LE were 4.92 mg/g and 9.58 mg/g, respectively. The electron donating ability and superoxide radical scavenging activity of ME were 84.32% and 76.34%, respectively. The oxygen radical absorbance capacity of the ME ($545.37{\mu}moles$ TE/g) was higher than LE ($427.18{\mu}moles$ TE/g). MMP-1 production in the HS68 cells were exposed to UVB suppressed by treatment with $200{\mu}g/mL$ of ME (68.6%) and LE (32.7%). ME and LE were applied to a skin aging mouse model, which was induced by the irradiation of UVB to the backs of hairless mice. The value of skin erythema index, wrinkle depth and thickness, epidermis thickness, and collagenous fiber damage in the experiment groups (MEL: ME 3%, MEM: ME 5%, MEH: ME 7%, LEL: LE 3%, LEM: LE 5%, LEH: LE 7%) were remarkably reduced than in the control group (only UVB exposure group), while water capacity increased. The level of total wrinkles depth in the skin was decreased to be 30% of the control group by MEH and LEM. These results suggest that ME and LE are useful cosmetic materials for skin protection against UVB-inducing.

• Herbal Formula Science
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• v.24 no.4
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• pp.243-257
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• 2016

Objectives : Illicium verum Hook. f. has been known to possess antimicrobial, antioxidant, antifungal, anti-inflammatory, insecticidal, analgesic, sedative, convulsive activities, it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Illicium verum Hook. f. water extracts (IVE) in vivo and in vitro. Methods : Cell viability was measured by MTT assay. The relative levels of NO were measured with Griess reagent. iNOS, COX-2, $NF-{\kappa}B$ and target proteins were detected by immunoblot analysis, and levels of cytokines were analyzed by ELISA kit. Anti-edema effect was determined in the carrageenan (CA)-induced paw edema model in rats. Results : All dosages of IVE used in MTT assay had no significant cytotoxicity. The increases of NO production and iNOS expression were detected in LPS-treated cells compared with control. However, these increases were attenuated by treatment with IVE. Also, IVE reduced the elevated production of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 by LPS. IVE inhibited the $p-I{\kappa}B$ and translocation of $NF-{\kappa}B$ to nuclear. Furthermore, IVE significantly inhibited the increases of hind paw swelling, skin thicknesses and inflammatory cell infiltrations induced by CA injection. Therefore, IVE will be favorably inhibited the acute edematous inflammations. Conclusion : These results provide evidences that anti-inflammatory effect of IVE is partly due to the reduction of some inflammatory mediators by suppression of $NF-{\kappa}B$ pathway.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.4
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• pp.1-13
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• 2019

Objective: This study is aimed to investigate the anti-tumor metastasis by innate immunomodulating effects of crude polysaccharide isolated from Polygonati Rhizoma (CP-PR) on 4T1 breast cancer cells. Methods: CP-PR was isolated from Polygonati Rhizoma. Antimetastatic experiments were conducted in vivo mouse model by using 4T1 breast cancer cells. The cell viability of CP-PR was tested with normal spleen and 4T1 breast cancer cells. To observe the activation of macrophages with/without 4T1 breast cancer cells, production of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), IL-10 and IL-12 were measured with enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the lysis of YAC-1 cells and the production of granzymes were measured to observe the activation of natural killer (NK) cell. Results: Intravenous administration of CP-PR significantly inhibited metastasis of 4T1 breast cancer cells. In an in vitro cytotoxicity analysis, CP-PR affected the growth of normal spleen and 4T1 breast cancer cells above specific concentration. The production of $TNF-{\alpha}$, IL-6, IL-10 and IL-12 were significantly increased in macrophages with CP-PR. As compared with control, CP-PR showed significantly higher production of $TNF-{\alpha}$, IL-10 and IL-12 in macrophages co-cultured with 4T1 breast cancer cells. The lysis of YAC-1 cells and the production of granzymes were significantly up regulated by CP-PR. Conclusion: CP-PR appears to have considerable activity on the anti-metastasis by activation of innate immune system.

• Journal of Life Science
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• v.32 no.5
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• pp.355-361
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• 2022

Melanin pigments are the main cause of skin color. They are produced in melanocytes and then transferred to keratinocytes, which eventually gives the skin surface a variety of colors. Although many skin-lightening or depigmenting agents have been developed, the demand for materials to reduce pig- mentation is still increasing. Here, we tried to find materials for skin-lightening or depigmentation using natural compounds and found that mistletoe (Viscum album var. coloratum) extracts (ME) had an inhibitory effect on tyrosinase activity. As a result, ME significantly reduced pigmentation in human primary melanocytes. In addition, a promoter reporter assay revealed that ME inhibited the transcription of microphthalmia-associated transcription factor (MITF), melanophilin (MLPH), tyrosinase-related protein-2 (TRP-2), and tyrosinase (TYR) genes in HM3KO melanoma cells. In addition, ME decreased the protein level for pigmentation-related molecules, such as TYR and TRP-1. Furthermore, it markedly inhibited the melanogenesis of zebrafish embryos, an in vivo evaluation model for pigmentation. To elucidate the action mechanism of ME, we investigated its effects on intracellular signaling. Eventually, the ME dramatically decreased the phosphorylation of the cAMP responsive element binding protein (CREB), AKT, and ERK. The data suggest that ME may inhibit the melanogenesis pathway by regulating the signaling pathway related to pigmentation. Taken together, these data propose that ME can be developed as a depigmenting or skin-lightening agent.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.40.1-40.24
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• 2022

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF^-CD11c^-CD11b⁺ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c^- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c^- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c^- monocytes did not. Ex vivo Ly6c^- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c^- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c^- monocytes could be a therapeutic target for asthma management.

• Journal of Life Science
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• v.33 no.12
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• pp.1036-1045
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• 2023

Sarcopenia, a condition characterized by the insidious loss of skeletal muscle mass and strength, represents a significant and growing healthcare challenge, impacting the mobility and quality of life of aging populations worldwide. This study investigated the therapeutic potential of soybean leaf extract (SL) for dexamethasone (Dexa)-induced muscle atrophy in vitro and in an in vivo model. In vitro experiments showed that SL significantly alleviated Dexa-induced atrophy in C2C12 myotube cells, as evidenced by preserved myotube morphology, density, and size. Moreover, SL treatment significantly reduced the mRNA and protein levels of muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (MAFbx), key factors regulating muscle atrophy. In a Dexa-induced atrophy mouse model, SL administration significantly inhibited Dexa-induced weight loss and muscle wasting, preserving the mass of the gastrocnemius and tibialis anterior muscles. Furthermore, mice treated with SL exhibited significant improvements in muscle function compared to their counterparts suffering from Dexa-induced muscle atrophy, as evidenced by a notable increase in grip strength and extended endurance on treadmill tests. Moreover, SL suppressed the expression of muscle atrophy-related proteins in skeletal muscle, highlighting its protective role against Dexa-induced muscle atrophy. These results suggest that SL has potential as a natural treatment for muscle-wasting conditions, such as sarcopenia.

• Korean Journal of Environmental Biology
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• v.29 no.3
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• pp.236-240
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• 2011

Mercury known as quicksilver, is the most common cause of heavy metal toxicity. Toxicity caused by excessive mercury exposure is now being recognized as a widespread environmental problem and is continuing to attract a great deal of public concerns. The mercury genotoxicity could be its effect on DNA repair mechanisms, which constitute the defense system designated to protect genome integrity. The objective of this study is to confirm that mercuric chloride inhibits the repair of gamma ray-induced DNA damage. The earthworm of Eisenia fetida was chosen for this study because it is an internationally accepted model species for toxicity testing with a cosmopolitan distribution. Experiments were done to identify the levels of DNA damage and the repair kinetics in the coelomocytes of E. fetida irradiated with 20 Gy gamma rays alone or with gamma rays after 40 mg $kg^{-1}$ $HgCl_2$ treatment by means of the single cell gel electrophoresis assay. The Olive tail moments were measured during 0~96 hours after irradiation. The repair time in the animals treated with the combination of $HgCl_2$ and ionizing radiation was nearly five times longer than that in the animals treated with ionizing radiation alone. Also, E. fetida exposed to mercury showed a statistically lower repair efficiency of gamma ray-induced DNA damage. The results suggest that the mercury could even have deleterious effects on the DNA repair system. Influence of mercury on the DNA repair mechanisms has been confirmed by this study.