• Journal of Gastric Cancer
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• v.21 no.4
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• pp.439-456
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• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.683-689
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• 2022

Background: Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were investigated in comparison with an extract of Korean Red Ginseng (ERG). Methods: In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl₃ (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H₂O₂) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B₂ production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed. Results: DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H₂O₂ cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B₂ production, and granule release, but also in delaying blood coagulation, FeCl₃-induced arterial occlusion, and thrombus formation. Conclusions: The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.83-91
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• 2024

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

• 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.

• BMB Reports
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• v.45 no.3
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• pp.141-146
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• 2012

Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPAR${\alpha}$ and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.698-704
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• 2019

Quercus mongolica (QM), which belongs to fagaceae, is one of the oak native to Korea. We evaluated the anti-inflammatory effect of branches extracted with 70% ethanol of QM (QM-B) and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. The QM-B showed anti-inflammatory activity through inhibition of NO production. The QM-B dose-dependently suppressed NO production by inhibiting iNOS, COX-2 and IL-6 expression in LPS-induced RAW264.7 cells. The QM-B inhibited the degradation and phosphorylation of IκB-α and NF-κB activation. The QM-B suppressed the phosphorylation of p38 and ERK1/2. Also, the QM-B increased HO-1 expression. These results suggested that QM-B may utilize anti-inflammatory activity by suppressing NF-κB and MAPK signaling pathway and inducing HO-1 expression indicated that the QM-B can be used as a natural anti-inflammatory drugs.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.48
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• pp.65-71
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• 2003

Sesame seed are one of the oldest oil-bearing crops known to man. Not only are they nutritious, they are physicologically beneficial. Because of these properties, the promotion of sesame as a crop is set to increase from now on. The lignan component of sesame, which has an antioxidative function, varies considerably. In addition, the seeds remain viable for longer than other crops. At low temperature, it has been reported that the seed remain viable for up to thirty years. This is due to the lignan content of the seeds. In the last twenty years, the mysteries of the natural chemistry of sesame seeds have been unravelled one by one. Up to now, the lignan component has been found to have an $\alpha$-tocopherol synergist effect, an anti-aging effect, a cancer suppressing effect, a hypertension reduction effect, an effect on the promotion of liver function, an effect on the control of the ration of unsaturated fat, and an effect on the synthesis of unsaturated fatty acids. The lignan component of sesame does not simply have an anti-oxidant function, but has diverse recently discovered physiological uses which make the study of lignan highly rewarding.

• The Korea Journal of Herbology
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• v.22 no.3
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• pp.67-76
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• 2007

Objectives : This study was carried out to know the effect of Cordyceps sinensis(CS) on the immune inflammatory responses of athritis and function. Methodes : To analyse immunomodulatory effects of CS, cytotoxicity and inhibition of proliferation against of synovial cells, gene expression of inflammatory mediators such as TNF-$\alpha$, IL-1$\beta$ and IL-6, DNA-binding activity of $NF-_{k}B$ and AP-1 were measured in vitro. Results : CS didn't show cytotoxicity against human synovial cells and inhibited proliferation of human synovial cells in a dose-dependent manner in combination with rIL-6. CS reduced the gene expression of IL-6 and IL-1$\beta$ in a dose- dependent manner but didn't reduced that of TNF-$\alpha$ in human synovial cells. CS reduced the binding-activity of $NF-_{k}B$ and also reduced that of AP-1 remarkably. Conclusion: We found out that Cordyceps sinensis has immunomodulatory effect of suppressing synovial cells. And Cordyceps sinensis will be used as a stable remedium in the auto-immune disease in the future.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.113-117
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• 2005

Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.

• Journal of Microbiology and Biotechnology
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• v.8 no.1
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• pp.74-80
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• 1998

CS-2l lymphoma cells that preferentially metastasize to lymph nodes after s.c. inoculation into BALB/c mice were grown in vitro in the presence of CA- 12 stromal cells isolated from lymph nodes. In order to obtain fundamental data on the identification and characterization of the soluble factors produced by CA-12 stromal cells, the conditioned medium of CA-12 stromal cells that inhibited apoptosis of CS-21 cells was examined. Various analytical treatments revealed that the soluble factors in CA-12 conditioned medium are very sensitive to heat treatment and trypsinization. Moreover CA-12 conditioned medium has an affinity with heparin but not with Con-A. In addition to these, the activity of CA-12 conditioned medium was blocked by H-7, a PKC inhibitor, but the conditioned medium could not induce the differentiation of thymocytes. We concluded that CA-12 conditioned medium contains stromal cell-derived apoptosis-inhibitory molecules that play an important role in proliferation of CS-2l cells by suppressing cell apoptosis.