• YAKHAK HOEJI
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• v.52 no.6
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• pp.500-506
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• 2008

Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. In this study we found that apigenin stimulated melanin synthesis in a dose-dependent manner in B16 murine melanoma cells. Since in our previous study $K^+$-$Cl^-$-cotransport (KCC) has been shown to mediate the mechanism of action of apigenin in neuronal cells, we further investigated the role of KCC in the melanogenesis-stimulating effect of apigenin in B16 cells. At nontoxic concentrations apigenin induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity, which was markedly prevented by a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that KCC is functionally present, and activated by apigenin in the B16 cells. In addition, the apigenin-induced stimulation of melanogenesis was also significantly inhibited by DIOA. NEthylmaleimide (NEM), a known KCC activator, induced $Cl^-$ efflux and stimulated melanogenesis in a concentration-dependent fashion. Both effects of NEM were significantly inhibited by DIOA. Taken together, these results suggest that apigenin can modulate melanogenesis through the activation of a membrane ion transporter, KCC in B16 cells. These results further suggest that apigenin may be a good candidate in the therapeutic strategy for hypopigmentation disorders, such as vitiligo.

• YAKHAK HOEJI
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• v.57 no.6
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• pp.388-393
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• 2013

Previously, we have reported that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, increased melanin synthesis through intracellular $Ca^{2+}$ release in B16 cells. In this study we investigated the possible involvement of nitric oxide (NO) in the mechanism of lovastatin-induced melanogenesis. Lovastatin elevated NO formation in a dose-dependent manner. Treatment with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), precursors of cholesterol, did not significantly alter the lovastatin-induced NO production, suggesting that inhibition of cholesterol metabolism may not be involved in the mechanism of this action of lovastatin. Both NO formation and melanogenesis induced by lovastatin was significantly suppressed by treatment with $N^G$-nitro-L-arginine methyl ester (L-NAME) and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide (cPTIO), an inhibitor of NO synthase and a NO scavenger, respectively. The lovastatin-induced NO production was significantly affected not by EGTA, an extracellular $Ca^{2+}$ chelator, but by an intracellular $Ca^{2+}$ chelator (BAPTA/AM) and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular $Ca^{2+}$ release in B16 cells. These results further suggest that lovastatin may be a good candidate for the therapeutic application of various hypopigmentation disorders.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.274-279
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• 2017

Objective: SanYangSam and SanYangSanSam are traditional Korea-medical herbs that are grown from Panax ginseng C.A. Meyer. In our previous studies, we found that the functional compounds in SanYangSam and SanYangSanSam were different and depended on the type and the cultivation environment of ginseng. This study aimed to profile the functional constituents in SanYangSam and SanYangSanSam. Methods: To profile the functional aspects of the many compounds that have therapeutic activities in SanYangSam and SanYangSanSam extracts, we used liquid chromatography tandem mass spectrometry and quadrupole orthogonal acceleration time-of-flight mass spectrometry. Results: A total of four major compounds were detected; two of which were the natural flavonoids kaempferol and quercetin. Among others, two polyacetylene compounds, including panaxydol and panaxynol, were detected. Conclusion: In this study, we found that panaxydol, one of the polyacetylene constituents of ginseng, is a candidate anti-cancer agent in SanYangSam and SanYangSanSam pharmacopuncture. In addition, we found that the panaxydol levels in the SanYangSanSam extract were over 30 times those in the SanYangSam extract.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.233-239
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• 1995

To verify the effect of immunosuppressants on the endotoxin-induced increase in iNOS activity, the action of immunosuppressants, dexamethasone (1.5 mg/kg), azathioprine (5 mg/kg/day) and cyclosporine (10 mg/kg), were evaluated in mice pretreated with LPS. The intraperitoneal injection of lipopolysaccharide (10 mg/kg) increased the nitric oxide synthase (NOS) activity in the brain and liver to maximum at 1 and 3 hours, respectively. The increase in NOS activity was blocked by the treatment with NOS inhibitor, LNAME(300 mg/kg) and aminoguanidine(100 mg/kg); a protein inhibitor, cycloheximide (10 mg/kg); and a transcription inhibitor of inducible NOS(iNOS), dexamethasone(1.5 mg/kg). Immunosuppressants, azathioprine (5 mg/kg) and cyclosporine (10 mg/kg), effectively blocked the increase in NOS activity. These results suggest that iNOS expression plays an important role in LPS-induced the increase in NOS activity and that immunosuppressants can be used as candidate for therapeutic agents in endotoxemia.

• Proceedings of the Korean Information Science Society Conference
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• 2007.10b
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• pp.17-21
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• 2007

Drug discovery is a long process with a low rate of successful new therapeutic discovery regardless of the advances in information technologies. Identification of candidate proteins is an essential step for the drug discovery and it usually requires considerable time and efforts in the drug discovery. The drug discovery is not a logical, but a fortuitous process. Nevertheless, considerable amount of information on drugs are accumulated in UniProt, NCBI, or DrugBank. As a result, it has become possible to try to devise new computational methods classifying drug target candidates extracting the common features of known drug target proteins. In this paper, we devise a method for drug target protein classification by using weighted feature summation and Support Vector Machine. According to our evaluation, the method is revealed to show moderate accuracy $85{\sim}90%$. This indicates that if the devised method is used appropriately, it can contribute in reducing the time and cost of the drug discovery process, particularly in identifying new drug target proteins.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.251-258
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• 2021

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 μM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 μM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

• Genomics & Informatics
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• v.19 no.1
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• pp.4.1-4.9
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• 2021

Lip and oral cavity cancer, which can occur in any part of the mouth, is the 11th most common type of cancer worldwide. The major obstacles to patients' survival are the poor prognosis, lack of specific biomarkers, and expensive therapeutic alternatives. This study aimed to identify the main genes and pathways associated with lip and oral cavity carcinoma using network analysis and to analyze its molecular mechanism and prognostic significance further. In this study, 472 genes causing lip and oral cavity carcinoma were retrieved from the DisGeNET database. A protein-protein interaction network was developed for network analysis using the STRING database. VEGFA, IL6, MAPK3, INS, TNF, MAPK8, MMP9, CXCL8, EGF, and PTGS2 were recognized as network hub genes using the maximum clique centrality algorithm available in cytoHubba, and nine potential drug candidates (ranibizumab, siltuximab, sulindac, pomalidomide, dexrazoxane, endostatin, pamidronic acid, cetuximab, and apricoxib) for lip and oral cavity cancer were identified from the DGIdb database. Gene enrichment analysis was also performed to identify the gene ontology categorization of cellular components, biological processes, molecular functions, and biological pathways. The genes identified in this study could furnish a new understanding of the underlying molecular mechanisms of carcinogenesis and provide more reliable biomarkers for early diagnosis, prognostication, and treatment of lip and oral cavity cancer.

• The Korean Journal of Oral and Maxillofacial Pathology
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• v.41 no.1
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• pp.1-7
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• 2017

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, was reported to various physiological and pharmacological effects including anti-cancer activity. Nevertheless, there is no report of the anticancer effect of lycorine in oral cancer cells. The effects of lycorine on cell proliferation and apoptosis were examined through trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole (DAPI) stain, Live/Dead assay, Western blot analysis and RT-PCR. Lycorine suppressed cell viability and induced apoptosis in MC3 and HSC-3 cell lines. Lycorine decreased survivin protein but did not affect its mRNA. It regulated survivin through accelerating protein degradation in a time-dependent manner although neither proteasome nor lysosome was not associated with lycorine-mediated protein degradation. Collectively, our results suggest that lycorine may be a potential therapeutic anti-cancer drug candidate for the treatment of human oral cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.93-93
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on GSK3${\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.92-92
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}$-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}$-catenin level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}$-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.