• 생명과학회지
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• 제29권2호
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• pp.181-190
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• 2019

시스템 약리학적 분석을 통해 대회향(Anisi Stellati Fructus)의 활성성분 스크리닝, 표적유전자 확보 및 관련 질병과의 네트워크를 구축한 후 대회향의 항균작용을 중점적으로 분석하였다. Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database 와 Analysis Platform을 통해 대회향의 잠재적 활성성분 49개를 확보하였으며, 그 중 설정한 조건에 부합하는 9개 활성성분을 스크리닝 하였다. TCMSP Database는 활성성분의 약물 동태학적 특성 및 약물-표적-질병 간의 관련성을 네트워크 수준에서 파악할 수 있는 획기적인 in silico적 접근을 가능하게 해준다. 활성성분과 반응하는 201개의 유전자 정보를 UniProt database를 통해 확인하고, 취합한 유전자들이 관여하는 348개의 생물학적 과정을 David 6.8 Gene Functional Classification Tool에서 확보하였다. Chemokine ligand 2, Interleukin-10, Interleukin-6, Tumor Necrosis Factor를 포함한 총 47개의 유전자가 항균작용에 관여하였고 이들을 표적으로 하는 luteolin, kaempferol, quercetin 등이 대표적 항균 관련 활성성분이었다. 이와 같이 확보된 데이터는 연구 재료 선정에 정확성과 시간, 노력, 비용 절감의 효과를 제공함과 더불어 추후 실험적 증명으로 이어져 감염병의 예방과 치료 전략에 과학적인 근거를 제시할 수 있을 것이다.

• 동의생리병리학회지
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• 제32권3호
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• pp.149-156
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• 2018

Traditional medicines (TM) in Korea, China, and Japan share most of the theories and therapeutic tools, but there are also differences due to their unique histories and cultures. Here, we aim to identify the differences in the utilization of TM theory between three countries by analyzing herb usage data in terms of the related traditional theories. Herb usage data of each country was collected from "Investigation of Korean medicine use and herbal medicine consumption survey" (Korea), "Analytical report on circulation of key Chinese medicinal materials" (China), and "Survey report on raw material crude drug usage" (Japan). Fifty five herbs with sixty features belonging to five theoretical categories (four properties, five tastes, targeting meridians, treatment strategies, and herbal parts) were selected and analyzed. Weight Sum Model (WSM) and Network-Based Group Features (NBGF) were used to compare the theoretical characteristics of TM between three countries. For the statistical evaluation, we developed and applied Herb Set Enrichment Analysis (HSEA) for WSM and NBGF results. HSEA for WSM results revealed the kidney meridian were targeted more in Korea than Japan, while the spleen meridian were targeted more in Japan than Korea. Herbs with sour taste were used more in Japan than China. HSEA for NBGF results found that NBGF including warm, neutral, sweet, and tonifying features were more dominant in Korea and than Japan, while NBGF including cold, bitter, heat-clearing features were more dominant in Japan than the others. These results suggest that TM in Korea, China, and Japan have unique aspects of practice patterns and theoretical utilization.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.288-292
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• 2009

Interactions between tumor cells and the extracellular matrix (ECM) strongly influence tumor development, affecting cell survival, proliferation and migration. Fibronectin, a major component of ECM, has been shown to interact with integrins especially the ${\alpha}5{\beta}1$ integrin. Cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs) which are capable of digesting the different components of the ECM and basement membrane. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated, resulting the 62 kDa active MMP-2. In this study, we investigated the effect of fibronectin on activation of pro-MMP-2 and the cellular invasiveness in H-Ras-transformed MCF10A human breast epithelial cells. Here we show that fibronectin induces activation of pro-MMP-2 and up-regulation of MT1-MMP and TIMP-2 in H-Ras MCF10A cells. These results demonstrate that H-Ras MCF10A cells secrete high levels of active MMP-2 when cultured with fibronectin, suggesting a possible interaction between the ECM network and H-Ras MCF10A cells to generate active MMP-2 which is important for proteolysis and ECM remodeling. Invasive and migratory abilities of H-Ras MCF10A cells were enhanced by fibronectin. Fibronectin up-regulated the expression of ${\beta}1$ integrin which may play a role in cellular responses exerted by fibronectin. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, this study provides a mechanism for the cell surface-matrix degrading effect of fibronectin which will be crucial to breast cell invasion and migration.

• IMMUNE NETWORK
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• 제12권3호
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• pp.113-117
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• 2012

FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

• IMMUNE NETWORK
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• 제10권5호
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• pp.173-180
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• 2010

Background: APRIL, originally known as a cytokine involved in B cell survival, is now known to regulate the inflammatory activation of macrophages. Although the signal initiated from APRIL has been demonstrated, its role in cellular activation is still not clear due to the presence of BAFF, a closely related member of TNF superfamily, which share same receptors (TACI and BCMA) with APRIL. Methods: Through transfection of siRNA, BAFF-deficient THP-1 cells (human macrophage-like cells) were generated and APRIL-mediated inflammatory activities were tested. The expression patterns of APRIL were also tested in vivo. Results: BAFF-deficient THP-1 cells responded to APRIL-stimulating agents such as monoclonal antibody against APRIL and soluble form of TACI or BCMA. Furthermore, co-incubation of the siBAFF-deficient THP-1 cells with a human B cell line (Ramos) resulted in an activation of THP-1 cells which was dependent on interactions between APRIL and TACI/BCMA. Immunohistochemical analysis of human pathologic samples detected the expression of both APRIL and TACI in macrophage-rich areas. Additionally, human macrophage primary culture expressed APRIL on the cell surface. Conclusion: These observations indicate that APRIL, which is expressed on macrophages in pathologic tissues with chronic inflammation, may mediate activation signals through its interaction with its counterparts via cell-to-cell interaction.

• IMMUNE NETWORK
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• 제9권3호
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• pp.90-97
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• 2009

Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation. Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface. Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-${\kappa}B$. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of $I{\kappa}B$, and nuclear translocation of NF-${\kappa}B$ p65 and p50 subunits. Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.238-245
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• 2022

Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 (Per2) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2-overexpressing (Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3, Hba-a1, and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward. Although encouraging further investigations, our findings suggest that these DEGs, including Asic3, may play significant roles in the lower sensitivity of Per2 OE mice to METH.

• Journal of Ginseng Research
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• 제46권2호
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• pp.175-182
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• 2022

Coronavirus disease 2019 (COVID-19) not only targets the respiratory system but also triggers a cytokine storm and a series of complications, such as gastrointestinal problems, acute kidney injury, and myocardial ischemia. The use of natural products has been utilized to ease the symptoms of COVID-19, and in some cases, to strengthen the immune system against COVID-19. Natural products are readily available and have been regularly consumed for various health benefits. COVID-19 has been reported to be associated with the risk of thromboembolism and deep vein thrombosis. These thrombotic complications often affects mortality and morbidity. Panax ginseng, which has been widely consumed for its various health benefits has also been reported for its therapeutic effects against cardiovascular disease, thrombosis and platelet aggregation. In this review, we propose that P. ginseng can be consumed as a supplementation against the various associated complications of COVID-19, especially against thrombosis. We utilized the network pharmacology approach to validate the potential therapeutic properties of P. ginseng against COVID-19 mediated thrombosis, the coagulation pathway and platelet aggregation. Additionally, we aimed to investigate the roles of P. ginseng against COVID-19 with the involvement of platelet-leukocyte aggregates in relation to immunity-related responses in COVID-19.

• Journal of Ginseng Research
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• 제47권4호
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• pp.524-533
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• 2023

Background: Obesity is a risk factor for aging and many diseases, and the disorder of lipid metabolism makes it prominent. This study aims to investigate the effect of ginsenoside Rg1 on aging, lipid metabolism and stress resistance Methods: Rg1 was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or GNGM. The lifespan, locomotory activity, lipid accumulation, cold and heat stress resistance and related mRNA expression of the worms were examined. Gene knockout mutants were used to clarify the effect on lipid metabolism of Rg1. GFP-binding mutants were used to observe the changes in protein expression Results: We reported that Rg1 reduced lipid accumulation and improved stress resistance in C. elegans. Rg1 significantly reduced the expression of fatty acid synthesis-related genes and lipid metabolism-related genes in C. elegans. However, Rg1 did not affect the fat storage in fat-5/fat-6 double mutant or nhr-49 mutant. Combined with network pharmacology, we clarified the possible pathways and targets of Rg1 in lipid metabolism. In addition, Rg1-treated C. elegans showed a higher expression of anti-oxidative genes and heat shock proteins, which might contribute to stress resistance Conclusion: Rg1 reduced fat accumulation by regulating lipid metabolism via nhr-49 and enhanced stress resistance by its antioxidant effect in C. elegans.

• IMMUNE NETWORK
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• 제16권2호
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• pp.140-145
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• 2016

Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.