• 약학회지
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• 제56권1호
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• pp.26-34
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• 2012

Mast cells play an important role in early and late phase allergic reactions through allergen and IgE-dependent release of histamine, proteases, prostaglandins, and several multifunctional cytokines. In this study, we investigated whether Cudrania tricuspidata extract (CTE) suppresses IgE-mediated allergic responses in mast cells, an allergic animal model, and its mechanism of action in mast cells. We found that CTE inhibited IgE-mediated degranulation and cytokine production in rat basophilic leukemia (RBL)-2H3 mast cells and bone marrow-derived mast cells (BMMC), as well as passive cutaneous anaphylaxis (PCA) in mice. With regard to its mechanism of action, CTE suppressed the activating phosphorylation of spleen tyrosine kinase (Syk), a key enzyme in mast cell signaling processes and that of LAT, a downstream adaptor molecule of Syk in $Fc{\varepsilon}RI$-mediated signal pathways. CTE also suppressed the activating phosphorylation of mitogen-activated protein (MAP) kinases and Akt. The present results strongly suggest that the anti-allergic activity of CTE is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Syk kinase in mast cells. Therefore, CTE may be useful for the treatment of allergic diseases.

• 한국약용작물학회지
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• 제15권6호
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• pp.451-456
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• 2007

Curcumin, a polyphenolic antioxidant purified from turmeric, has been known to possess various biological activities such as anti-oxidative, anti-inflammatory and anti-cancer effects. In this study, we have explored anti-inflammatory effect of curcumin using Gram (-) bacterium-derived endotoxin (lipopolysaccharide: LPS) and macrophage cell line RAW264.7. Curcumin suppressed NO production in LPS-activated RAW264.7 cells in a dose-dependent manner, Curcumin also blocked the activation of $NF-{\kappa}B$ but not AP-1 according to luciferase assay. Furthermore, this compound suppressed the phosphorylation of a series of intracellular signaling components such as Src, JAK-2, Akt, IKK and $I{\kappa}B{\alpha}$ under LPS stimulation in a time dependent manner, Therefore, our data suggest that curcumin was able to protect the host from Gram(-) bacterial-infection-mediated inflammatory symptoms.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.411-418
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• 2011

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including $p27^{Kip1}$ and $p21^{WAF1/Cip1}$, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and $p70^{S6K}$. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.

• Journal of Applied Biological Chemistry
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• 제64권3호
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• pp.317-322
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• 2021

Among the different cardiovascular disorders (CVDs), the activation of platelets is a necessary step. Based on this knowledge, therapeutic treatments for CVDs that target the disruption of platelet activation are proving to be worthwhile. One such substance, a bioactive 6,7-dihydroxy derived from coumarin, is 6,7-Dihydroxy-2H-1-benzopyran-2-one (esculetin). This compound has demonstrated several pharmacological effects on CVDS as well as various other disorders including diabetes, obesity, and renal failure. In various reports, esculetin and its effect has been explored in experimental mouse models, human platelet activation, esculetin-inhibited collagen, and washed human platelets exhibiting aggregation via arachidonic acid. Yet, esculetin affected aggregation with agonists like U46619 or thrombin in no way. This study investigated esculetin and how it affected human platelet aggregation activated through U46619. Ultimately, we confirmed that esculetin had an effect on the aggregation of human platelets when induced from U46619 and clarified the mechanism. Esculetin interacts with the downregulation of both phosphoinositide 3-kinase/Akt and mitogen-activated protein kinases, important phosphoproteins that are involved in activating platelets and their signaling process. The effects of esculetin reduced TXA₂ production, phospholipase A₂ activation, and platelet secretion of intracellular granules (ATP/serotonin), ultimately causing inhibition of overall platelet aggregation. These results clearly define the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

• 생약학회지
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• 제52권3호
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• pp.127-133
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• 2021

Platelet activation plays a major role in cardiovascular disorders (CVDs). Thus, disrupting platelet activation represents an attractive therapeutic target on CVDs. Esculetin, a bioactive 6,7-dihydroxy derivative of coumarin, possesses pharmacological activities against obesity, diabetes, renal failure, and CVDs. In other report, the effect of esculetin has been examined in human platelet activation and experimental mouse models, and esculetin inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets. However, it had no effects on other agonists such as thrombin and U46619, and its mechanism is not also clearly known. This study investigated the effect of esculetin on collagen-induced human platelet aggregation, and we clarified the mechanism. Esuletin has effects on the down regulation of PI3K/Akt and MAPK, phosphoproteins that act in the signaling process in platelet aggregation. The effects of esculetin reduced of TXA₂ production and phospholipase A₂ activation, and intracellular granule secretion including ATP and serotonin, leading to inhibit platelet aggregation. These results clearly clarified the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

• 한국발생생물학회지:발생과생식
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• 제25권1호
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• pp.67-72
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• 2021

This study investigated the IGF-1 signal in specific tissues using Pacific oysters artificially matured via water temperature elevation. Pacific oysters were subjected to water temperature elevation from March to June, and 20 were randomly sampled each month. The condition index (CI) and tissue weight rate (TWR) were examined by measuring shell length, shell height, shell width, and soft tissue weight. The IGF-1 signal in tissues (adductor muscle, digestive glands, gills, labial palps, mantle edges, and gonads) was analyzed by sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. From April to June, the TWR of females and males increased from 19.1±2.9 to 21.0±3.6 and 18.2±2.0 to 19.2±2.5, respectively, while the CI remained the same. The IGF-1 signal in each tissue differed. IGF-1 was expressed in the adductor muscle, while tyrosine was expressed in all tissues. The phosphor (p)-ERK and p-AKT activities were high in the adductor muscle, mantle edge, and gonads. IGF-1 signaling affected the growth and maturity of the Pacific oysters examined.

• 한국미생물·생명공학회지
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• 제49권4호
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• pp.594-602
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• 2021

The NLRP3 (nucleotide-binding domain, leucine-rich repeat family pyrin domain containing 3) inflammasome plays an important role in the initiation of inflammatory responses, through the recognition of pathogen-associated molecular patterns and tumor progression, including tumor growth and metastasis. In this study, we examined the effects of defective NLRP3 on the growth, migration, and invasiveness of hepatocellular carcinoma (HCC) SK-Hep1 cell. First, HCC SK-Hep1 cells were transfected with human NLRP3 targeting LentiCRISPRv2 vector using the CRISPR-Cas9 system, and NLRP3 deficiency was confirmed by RT-qPCR and western blotting. NLRP3 deficient SK-Hep1 cells showed delayed cell growth and decreased protein expression of PI3K, p-AKT, and pNF-κB when compared to NLRP3 complete SK-Hep1 cells. In addition, NLRP3 deficiency arrested the cell cycle at G1 phase through an increase in p21 and a reduction in CDK6. NLRP3 deficient SK-Hep1 cells also showed significantly delayed cell migration, invasion, and wound healing. The expression of epithelial-mesenchymal transition signaling molecules, such as N-cadherin and MMP-9, was found to be dramatically decreased in NLRP3 deficient SK-Hep1 cells compared to NLRP3 complete SK-Hep1 cells.

• 대한의생명과학회지
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• 제28권2호
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• pp.92-100
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• 2022

Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anti-cancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

• Journal of Microbiology and Biotechnology
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• 제32권8호
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• pp.982-988
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• 2022

Licorice (Glycyrrhiza) has been used as preventive and therapeutic material for hyperpigmentation disorders. Previously, we isolated noble compounds including dehydroglyasperin C (DGC), dehydroglyasperin D (DGD) and isoangustone A (IAA) from licorice hexane/ethanol extracts. However, their anti-melanogenic effects and underlying molecular mechanisms are unknown. The present study compared effects of DGC, DGD and IAA on pigmentation in melan-a melanocytes and human epidermal melanocytes (HEMn). DGD exerted the most excellent anti-melanogenic effect, followed by DGC and IAA at non-cytotoxic concentrations. In addition, DGD significantly inhibited tyrosinase activity in vitro cell-free system and cell system. Western blot result showed that DGD decreased expression of microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related protein-1 (TRP-1) in melan-a cells and HEMn cells. DGD induced phosphorylation of MITF, ERK and Akt signal pathway promoting MITF degradation system. However, DGD did not influence p38 and cAMP-dependent protein kinase (PKA)/CREB signal pathway in melan-a cells. These result indicated that DGD inhibited melanogenesis not only direct regulation of tyrosinase but also modulating intracellular signaling related with MITF level. Collectively, these results suggested a protective role for DGD against melanogenesis.

• Journal of Ginseng Research
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• 제46권2호
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• pp.206-213
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• 2022

Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.