• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.203-213
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• 2018

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

• Food Science and Preservation
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• v.23 no.3
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• pp.378-386
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• 2016

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

• Journal of Life Science
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• v.33 no.6
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• pp.471-480
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• 2023

This study was designed to evaluate the anti-inflammatory effects of Rumohra adiantiformis extracts fermented with Bovista plumbea mycelium (B-RAE) in LPS-stimulated RAW 264.7 cells. The total polyphenol and total flavonoid content of B-RAE were 379.26±7.77 mg/g and 50.85±3.08 mg/g, respectively. The results of measuring the antioxidant activity of B-RAE showed that it scavenges 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and superoxide anion radical in a dose-dependent manner. B-RAE inhibited nitric oxide (NO) production in a dose-dependent manner without affecting cell viability. The gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-lβ (IL-1β), and IL-6 was measured using real time quantitative reverse transcription PCR (qRT-PCR). We found that, compared to the LPS-treated group, B-RAE significantly reduced the mRNA levels of the pro-inflammatory cytokines in a concentration-dependent manner. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the phosphorylation of transcription factors such as nuclear factor-κB (NF-κB), and the mitogen-activated protein kinase (MAPK) signaling pathway proteins were assessed using Western blot analysis. We found that B-RAE significantly suppressed the expression of iNOS and COX-2, but their expression was increased by LPS treatment. In addition, the phosphorylation of NF-κB and IκB, which was increased by LPS treatment, was reduced with B-RAE treatment. The effect of B-RAE on the phosphorylation of the MAPK signaling pathway proteins was measured, and the phosphorylation of extracellular signal-regulated kinase (ERK) and the p38 MAPK proteins decreased in a dose-dependent manner, while the phosphorylation of c-Jun N-terminal kinase (JNK) increased. These anti-inflammatory effects of B-RAE may thus have been achieved through the high antioxidant activity, the inhibition of NO production through the suppression of iNOS and COX-2 expression, the inhibition of the NF-κB pathway, and the suppression of pro-inflammatory cytokine expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.206-213
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• 2009

Sophora flavescens, as a traditional herbal medicine, has been used to treat with a variety of disesases, In previous reports, S. flavescens and sophoraflavanone G (a prenylated flavonoid from S. flavescens) inhibited cytokines productions in LPS-induced Raw 264.7 macrophages cells and BV2 microglial cells. We examined on the anti-allergic effect of S. flavescens on the PMA plus A23187-induced rat leukemia (RBL-2H3) cells. S. flavescens inhibited the release of $\beta$-hexosaminidase and productions and expressions of tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-4 and cyclooxygenase (COX)-2 in a dose-dependent manner on stimulated RBL-2H3 cells, however, S. flavescens not affect cell viability. The protein expression level of nuclear factor (NF)-${\kappa}B$ (p65) was decreased in the nucleus and suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein, the activation of extracellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK) by S. flavescens. These results suggest that S. flavescens could be involved anti-allergic effect by control of $NF-{\kappa}B$ (p65) translocation into the nucleus through inhibition of $I{\kappa}B-{\alpha}$ degradation and suppression of pro-inflammatory cytokines expression.

• The Korean Journal of Malacology
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• v.30 no.2
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• pp.155-163
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• 2014

Serpins are a group of proteins involved in the regulation of serine and other type of proteases, and have been identified in many kinds of organisms from invertebrates to vertebrates. Serpins are known to regulate the proteolytic cascades of the innate immune pathways in addition to their roles in blood coagulation, angiogenesis, fibrinolysis, inflammation and tumor suppression. In this study, we have isolated two partial serpin gene fragments from expressed sequence tags (ESTs) of Nesiohelix samarangae. Dotplot analysis indicates that they are of two different types, Ns-serpin type 1 and Ns-serpin type 2. Ns-serpin type 1 has 819 bp coding region (272 amino acids), whereas Ns-serpin type 2 has 555 bp coding region (185 amino acids). Molecular phylogenetic analysis shows that the identified serpins have high similarities to their counterparts in the California see slug, Aplysia californica. Yet, the precise biological and immunological roles of these Ns-serpins remain to be further investigated using RNA interference and other molecular techniques.

• Journal of Life Science
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• v.19 no.4
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• pp.502-507
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• 2009

In modern oriental medicine, bee venom therapy is being used for aqua-acupuncture to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout. Bee venom therapy has been processed and reported in many experimental studies, with regard to its effects on pain alleviation, anti-inflammation, removal of fever, anti-convulsion, suppression of tumor and immunity strengthening, etc., however, its mechanism of action, molecular targeting on prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remains unclear. In this study, we investigated the effect of bee venom on the levels of cyclooxygenases (COXs) and telomere regulatory components of A549 human lung cancer cells. Bee venom-induced anti-proliferative effects of A549 cells were associated with the inhibition of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR), transcription factor c-myc and the activity of telomerase. In addition, bee venom treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of bee venom.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.1008-1013
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• 2011

Osteoporosis is the leading underlying cause of fractures, particularly in postmenopausal women, due to the loss of estrogen-mediated suppression of bone resorption. More than 50% of adults 50 years of age or older are estimated to have osteoporosis. Osteoclast which is main target for treatment of osteoporosis is originated from hematopoietic cell line. Aloe has been widely used in worldwide country as a coadjuvant medicine. Extracts of the leaves of Aloe have been used in condition to improve dermatologic problem such as seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus and has been known to exert anti-inflammatory, anti-oxidant and anti-tumor effects. However, despite the popularity of aloe as a plant food supplements, the evaluation of its efficacy as a possible therapeutic option for osteoporosis remains scarce. Thus, we evaluated the effect of Aloe on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Here we found that Aloe significantly inhibited osteoclast differentiation induced by RANKL. Aloe suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Aloe significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Aloe greatly inhibited the protein expression of c-fos and NFATc1. Taken together, our results suggested that Aloe may be useful tool for treatment of osteoporosis by inhibition of osteoclast differentiation.

• Korean Journal of Food Science and Technology
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• v.47 no.1
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• pp.119-125
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• 2015

The aim of this study was to investigate the synergistic anti-inflammatory effect of rosmarinic acid (RA) and luteolin from perilla (Perilla frutescens L.) leaves in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. A combination of RA and luteolin more strongly inhibited the production of nitric oxide (NO), inducible NOS (iNOS), prostaglandin $E_2$ ($PGE_2$), and COX-2 than higher concentrations of RA or luteolin alone in LPS-stimulated RAW264.7 macrophages. The combined RA and luteolin synergistically inhibited the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and interleukin-$1{\beta}$ (IL-$1{\beta}$), in LPS-stimulated RAW264.7 macrophages. Furthermore, combined RA and luteolin more strongly suppressed NF-${\kappa}B$ activation than RA or luteolin alone, by inhibiting the degradation of inhibitor of NF-${\kappa}B(I{\kappa}B)$-${\alpha}$ and nuclear translocation of the p65 subunit of NF-${\kappa}B$ in LPS-stimulated RAW264.7 macrophages. Collectively, these results suggest that RA and luteolin in combination exhibit synergistic effects in suppression of LPS-induced inflammation in RAW264.7 macrophages.

• ALGAE
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• v.29 no.4
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• pp.355-366
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• 2014

Fucoxanthin is known to be an effective cell proliferation inhibitor with anti-tumor and anti-angiogenic activities. However, there is a lack of data regarding the biological effects of cis isomers of fucoxanthin. To assess the potential therapeutic properties of 9'-cis-(6'R) fucoxanthin (FcA), and 13-cis and 13'-cis-(6'R) fucoxanthin complex (FcB) isolated from Sarggassum siliquastrum, we investigated their inhibitory effects on matrix metalloproteinases (MMPs) in phorbol 12-myristate 13-acetate (PMA)-induced human fibrosarcoma (HT1080) cells. FcA and FcB reduced MMP-2 and MMP-9 protein and mRNA levels, as well as the migration of these cells, in a dose-dependent manner. Additionally, FcA and FcB increased levels of MMPs inhibition factors such as tissue inhibitor of metalloproteinase-1. FcA and FcB significantly inhibited the transcriptional activity of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) and by inhibiting c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases. Our results demonstrate that suppression of the NF-${\kappa}B$, JNK, and p38 signaling pathways may inhibit PMA-induced MMP-2 and MMP-9 activity. Therefore, FcA and FcB may be useful in noninvasive therapeutic strategies against fibrosarcoma metastasis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.181-187
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• 2016

Algae is a potential resource with various biological activities. In this study, the anti-inflammatory effect of Grateloupia imbricata Holmes ethanol extract (GIHEE) from red algae was investigated in LPS-induced RAW 264.7 cells. As a result, reduced secretion of pro-inflammatory cytokines [tumor necrosis factors-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6] and nitric oxide (NO) was observed in a dose-dependent manner. Expression of nuclear factor-kappaB (NF-${\kappa}B$) as well as inducible NO synthase and cyclooxygenase-2 proteins was reduced by GIHEE, suggesting that the anti-inflammatory activity of GIHEE is related to suppression of NF-${\kappa}B$ signaling pathways. In addition, GIHEE reduced phosphorylation of mitogen-activated protein kinases. These results suggest that GIHEE can be used as a potential anti-inflammatory therapeutic.