• Journal of Microbiology and Biotechnology
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• 제24권11호
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• pp.1583-1591
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• 2014

Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVB-induced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent.

• Journal of Ginseng Research
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• 제36권1호
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• pp.86-92
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• 2012

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권1호
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• pp.10-23
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• 2007

Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.

• Journal of Ginseng Research
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• 제44권1호
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• pp.145-153
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• 2020

Background: Panax ginseng Meyer (Araliaceae) is a highly valued medicinal plant in Asian regions, especially in Korea, China, and Japan. Chemical and biological studies on P. ginseng have focused primarily on its roots, whereas the seeds remain poorly understood. This study explores the phytochemical and biological properties of compounds from P. ginseng seeds. Methods: P. ginseng seeds were extracted with methanol, and 16 compounds were isolated using various chromatographic methods. The chemical structures of the isolates were determined by spectroscopic data. Antiinflammatory activities were evaluated for triterpene and steroidal saponins using lipopolysaccharide-stimulated RAW264.7 macrophages and THP-1 monocyte leukemia cells. Results: Phytochemical investigation of P. ginseng seeds led to the isolation of a novel triterpene saponin, pseudoginsenoside RT₈, along with 15 known compounds. Pseudoginsenoside RT₈ exhibited more potent antiinflammatory activity than the other saponins, attenuating lipopolysaccharide-mediated induction of proinflammatory genes such as interleukin-1β, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-9, and suppressed reactive oxygen species and nitric oxide generation in a dose-dependent manner. Conclusion: These findings indicate that pseudoginsenoside RT₈ has a pharmaceutical potential as an antiinflammatory agent and that P. ginseng seeds are a good natural source for discovering novel bioactive molecules.

• 대한한의학회지
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• 제39권4호
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• pp.86-113
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• 2018

Objectives: We examined the effects of a mixed formula consisting of dried pomegranate concentrate powder (PCP) and the aqueous extracts of Eucommiae cortex (EC) and Achyranthis radix (AR) in rats with surgically induced osteoarthritis (OA). Methods: Two weeks after OA-inducing surgery, a PCP:EC:AR 5:4:1 (g/g) combination or single formula was orally administered. Changes in body weight, knee thickness, maximum knee extension angle, bone mineral density of the knee joints, femoral and tibial articular surfaces, and compressive strength of the femoral and tibial articular cartilage (AC) were assessed, along with the prostaglandin E2 level, 5-lipoxygenase, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and chondrogenic gene mRNA expression in the femoral and tibial AC with the synovial membrane (SM). In addition, the number of cleaved poly(ADP-ribose) polymerase, cyclooxygenase and tumor necrosis factor-${\alpha}$-immunoreactive cells in the femoral and tibial AC with SM were monitored, and the rate of cell proliferation was determined with a 5-bromo-2'-deoxyuridine uptake assay. Results : The signs of surgically induced OA in rats were significantly inhibited by both PCP, EC and AR combined and single formulas. In particular, the combination formula-treated OA model rats showed dose-dependent, significantly increased inhibitory activity against all tested criteria compared with single formula-treated rats. Conclusions: Taken together, our results suggest that the combination formula synergistically increased the anti-OA effects of its components through anti-inflammatory and chondrogenic activity in rats with surgically induced OA. In addition, 200, 100 and 50 mg/kg combination formula treatments showed dose-dependent inhibitory activity against all of the tested criteria.

• 한국약용작물학회지
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• 제27권2호
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• pp.143-150
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• 2019

Background: Skin is an organ that protects the human body from various environmental stimuli that can induce immune system activation. Skin aging can be largely divided into two categories: physiological aging, which is caused by the a decreased physiological function of the skin and structural changes with aging, and photoaging, which is caused by the chemical stress induced by external stimuli such as ultraviolet (UV) radiation. Methods and Results: The objective of this study was to investigate the anti-wrinkle and UV protective effect of catechin-rich green tea extract (CGTE) in activated keratinocyte (HaCaT cells) and UV-induced skin damage in hairless mice. The results showed that CGTE inhibits the tumor necrosis factor-alpha interferon-gamma ($TNF-{\alpha}+IFN-{\gamma}$)-induced expression of matrix metalloproteinase (MMP)-1 in HaCaT cells. In addition, the CGTE treatment significantly reduced wrinkle formation, epidermal thickness, collagen deposition, and transepidermal water loss in dorsal skin irradiated with UVB. However, the ${\beta}$-glucosidase activity was significantly increased. The CGTE treatment inhibits mRNA expression and enzyme activity of MMP-2 and MMP-9 in the dorsal skin irradiated with UVB. Conclusions: It is expected that CGTE can be effectively used as a functional food and cosmetic ingredient to improve skin moisture retention and reduce wrinkle formation.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.380-388
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• 2022

Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

• 대한본초학회지
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• 제28권3호
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• pp.1-5
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• 2013

Objectives : This study was designed to investigate the collagen metabolism and tyrosinase activity of Polygonati Rhizoma extracts (PR). It's effects are to tonify spleen qi and augment the spleen yin. It enrichs the yin and moisten the lung. Methods : The effect of PR on type I procollagen production and collagenase (matrix metalloproteinase-1, henceforth referred as MMP-1) activity in human normal fibroblasts Hs68 after ultraviolet B (UVB, 312 nm) irradiation was measured by ELISA method. The tyrosinase activity after treatment of PR was measured. Results : There were no cytotoxicity at concentrations of 10, 30, $100{\mu}g/ml$. The reduced type I procollagen production was recovered by PR in UVB damaged Hs68 cells at a concentration of $100{\mu}g/ml$ ($16.2{\pm}0.0$ ng/ml) from control group ($13.9{\pm}0.5$ ng/ml). However there was no statistical significance. PR reduced The increased MMP-1 activity after UVB damage at concentrations of $10{\mu}g/ml$, $30{\mu}g/ml$, and $100{\mu}g/ml$ in a dose dependent manner ($42.2{\pm}20.5%$, $44.8{\pm}8.5%$, and $22.0{\pm}5.8%$). PR $100{\mu}g/ml$ treatment showed the statistical significace (p < 0.05). PR significantly reduced the tyrosinase activity at a concentration of 10 mg/ml ($32.0{\pm}12.8%$, p < 0.05). However, the L-DOPA oxidation was not changed. Conclusion : PR showed the anti-wrinkle effects and whitening effects in vitro. Although more researches are needed to validate the efficacy, these results suggest that PR may have potential as an anti-aging ingredient in cosmetic herb markets.

• Journal of Ginseng Research
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• 제46권1호
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• pp.167-174
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• 2022

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. Methods: CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. Results: We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Conclusion: Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.

• 대한통합의학회지
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• 제11권3호
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.