• Journal of Ginseng Research
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• v.48 no.2
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• pp.211-219
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• 2024

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 10⁹ particles/mL), and followed by UVB irradiation or H₂O₂ exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.161-168
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• 2012

The abnormal maturation and ossification of articular chondrocytes play a central role in the pathogenesis of osteoarthritis (OA). Inhibiting the enzymatic degradation of the extracellular matrix and maintaining the cellular phenotype are two of the major goals of interest in managing OA. Ginseng is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. Ginsenoside $Rb_1$, a major component of ginseng that contains an aglycone with a dammarane skeleton, has been reported to exhibit various biological activities, including anti-inflammatory and anti-tumor effects. However, a chondroprotective effect of ginsenoside $Rb_1$ related to OA has not yet been reported. The purpose of this study was to demonstrate the chondroprotective effect of ginsenoside $Rb_1$ on the regulation of pro-inflammatory factors and chondrogenic genes. Cultured rat articular chondrocytes were treated with 100 ${\mu}M$ ginsenoside $Rb_1$ and/or 500 ${\mu}M$ hydrogen peroxide ($H_2O_2$) and assessed for viability, reactive oxygen species production, nitric oxide (NO) release, and chondrogenic gene expression. Ginsenoside $Rb_1$ treatment resulted in reductions in the levels of pro-inflammatory cytokine and NO in $H_2O_2$-treated chondrocytes. The expression levels of chondrogenic genes, such as type II collagen and SOX9, were increased in the presence of ginsenoside $Rb_1$, whereas the expression levels of inflammatory genes related to chondrocytes, such as MMP1 and MMP13, were reduced by approximately 50%. These results suggest that ginsenoside $Rb_1$ has potential for use as a therapeutic agent in OA patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.971-977
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• 2015

Malignant glioblastoma multiforme (GBM) is the most malignant brain tumor and despite recent advances in diagnostics and treatment prognosis remains poor. In this retrospective study, we assessed the clinical and radiological parameters, as well as fluorescence in situ hybridization (FISH) of 1p19q deletion, in a series of cases. A total of 816 patients with GBM who received surgery and radiation between January 2010 and May 2014 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patient progression free survival (PFS) and overall survival (OS). Age at diagnosis, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 and MMP9 expression level and adjuvant chemotherapy were statistically significant factors (p<0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age ${\leq}50$ years, preoperative KPS score ${\geq}80$, KPS score change after operation ${\geq}0$, involvement of single frontal lobe, deep structure involvement, low Ki-67 and MMP9 expression and adjuvant chemotherapy were independent favorable factors (p<0.05) for patient clinical outcomes.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.4
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• pp.365-373
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• 2023

Since the lips are a representative facial part that can express human attraction, aesthetic interest in them has always existed in human history. However, as lips age, they tend to form wrinkles, become thinner, and lose their volume. To counteract this phenomenon, medical procedures such as fillers or fat transplantation have been suggested. In this study, we verified that the one of main effective material complex of L G H&H L IPCERIN^®, combination of cedrol, a sesquiterpene found in cedarwood, and three peptides (acetyl hexapeptide-8, acetyl tetrapeptide-9, and desamidocollagen) could ameliorate the photo-aging and reduce the wrinkles through in vitro experiments. The possibility of improving collagen and elastin expression in skin fibroblasts and reducing MMP expression under photoaging conditions was verified. In addition, it was confirmed that the amount of fat tissue in the lips can be increased by promoting adipose stem cell differentiation and increasing the amount of fat produced in the in vitro adipose stem cell differentiation experiment. Two weeks of human application tests confirmed that a combination of cedrol and peptides can improve the wrinkles, texture, elasticity, and volume of the lips. This study verified that the combination of cedrol and three peptides can be used as effective cosmetic materials to decrease the various signs of aging in the lips.

• Journal of Society of Preventive Korean Medicine
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• v.19 no.2
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• pp.135-144
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• 2015

Objective : Saengmaek-san (SM) has been commonly used in Korea to treat various diseases that involve the respiratory and cardiovascular system. However, to date, the mechanism underlying the effects of osteoclasts differentiation of SM has not been clearly understood. Method : To evaluate the effect of SM on osteoclast differentiation, we induced RAW 264.7 cells to be differentiated to osteoclasts by RANKL, and we performed RT-PCR to measure gene expression. Results : SM decreased the number of TRAP(+) MNCs in RANKL-induced osteoclast. SM decreased the expression of MMP-9, cathepsin K1, TRAP, NFATc1, MITF, and COX-2 in the osteoclast. But SM increased the expression of iNOS, $TNF-{\alpha}$ and IL-6 in osteoclast. Conclusion : It is concluded that SM might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.74-74
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• 2020

Skin is continuously exposed to a variety of environmental stresses, including ultraviolet (UV) radiation. UVB is an inherent component of sunlight that crosses the epidermis and reaches the upper dermis, leading to increased oxidative stress, activation of inflammatory response and accumulation of DNA damage among other effects. In the present study, the anti-wrinkle mechanism of Acorus gramineus callus culture supernatant (GB-AGS-PSC) was elucidated in UVB treated HaCaT keratinocytes. GB-AGS-PSC prevented the matrix metalloprotease 1 (MMP-1), elastin, and pro-collagen product and cytotoxicity and SOD inhibition. Quantitative polymerase chain reaction showed that GB-AGS-PSC-treated cells displayed dose-dependent increase in messenger RNA expression levels of Aquaporin 3 (AQP3), Keratin 1(KRT1), fillagrin, and hyaluronan synthase-2 (HAS 2) and decreased expression levels of matrix metalloproteinase-3, -9, and -13 in UVB treated HaCaT keratinocytes. Additionally, GB-AGS-PSC suppressed TNF-α, IL-1β, and IL-8 product for inflammatory responses in UVB treated HaCaT keratinocytes. Therefore, GB-AGS-PSC may be useful as an anti-photoaging resource for the skin.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.830-838
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• 2020

The present study aimed to evaluate the effect of radiation mutant Perilla frutescens var. crispa on bone metabolism and the inflammatory response in a monosodium iodoacetateinduced rat model of osteoarthritis. radiation mutant Perilla frutescens var. crispa was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 μl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral radiation mutant Perilla frutescens var. crispa for another 4 weeks. It was evaluated that the treatment effects based on serum biomarkers, and morphological and histopathological analysis of the knee joints. Compared with those in control rats, the radiation mutant Perilla frutescens var. crispa treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., COX-2, LTB4, MMP-3, and COMP), and the amount of fibrous tissue. Otherwise, it was significantly increased the concentration of TIMP-1 and calcitonin. In addition, the radiation mutant Perilla frutescens var. crispa treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that radiation mutant Perilla frutescens var. crispa prevented and alleviated osteoarthritis symptoms. Thus, radiation mutant Perilla frutescens var. crispa can be used in food and drug material for the management of osteoarthritis.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.52-58
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• 2011

The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of inflammation-related genes, including IL-$1\beta$, IL-6, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of inflammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-$1\beta$, representative inflammatory genes, were confirmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of inflammation-associated genes.

• Korean Journal of Plant Resources
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• v.32 no.4
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• pp.255-263
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• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and Glycyrrhizae radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of programed cell death (apoptosis) by Glycyrrhizae radix are poorly defined. In the present study, it was examined the molecular mechanisms of apoptosis by water extracts of Glycyrrhizae radix (GRW) in human bladder T24 cancer cells. It was found that GRW could inhibit the cell growth of T24 cells in a concentration-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by GRW was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL), and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of GRW induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of PARP. GRW also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that GRW may be a potential chemotherapeutic agent for the control of human bladder cancer cells.