• IMMUNE NETWORK
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• v.10 no.2
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• pp.55-63
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• 2010

Background: Cordyceps militaris has been used in traditional medicine to treat numerous diseases and has been reported to possess both antitumor and immunomodulatory activities in vitro and in vivo. However, the pharmacological and biochemical mechanisms of Cordyceps militaris extract (CME) on macrophages have not been clearly elucidated. In the present study, we examined how CME induces the production of proinflammatory cytokines, transcription factor, and the expression of co-stimulatory molecules. Methods: We confirmed the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecules. Results: CME dose dependently increased the production of NO and proinflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, and it induced the protein levels of iNOS, COX-2, and proinflammatory cytokines in a concentrationdependent manner, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 was also enhanced by CME. Furthermore, the activation of the nuclear transcription factor, NF-${\kappa}B$ in macrophages was stimulated by CME. Conclusion: Based on these observations, CME increased proinflammatory cytokines through the activation of NF-${\kappa}B$, further suggesting that CME may prove useful as an immune-enhancing agent in the treatment of immunological disease.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1544-1553
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/ml$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited cell adhesion that non-activated U937 monocytic cell adhesion to HUVECs activated with $IL-1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with $IL-1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to $IL-1{\beta}$-stimulated HUVECs was completely suppressed by 121% at a concentration of $18.5{\mu}g/ml$. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin, and VE-cadherin to NF-kB, based on western bolt analysis. It also inhibited IL-l-stimulated HUVEC expression of the adhesion molecules, ICAM-l by 40%, VCAM-l by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities, and non-toxicity may be expected from these results.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.299-307
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• 2015

Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

• The Korea Journal of Herbology
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• v.33 no.6
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• pp.79-86
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• 2018

Objectives : Hemorrhoids are one of the most common diseases in humans. Jingyoganghwaltang (JG) and Cheongsimhwan (CS) have been used for treating hemorrhoids in Korean traditional clinical practice. The present study was designed to evaluate the traditional effects of JG and CS on the experimental hemorrhoid model in rats. Methods : Hemorrhoids are closely related to inflammation. Accordingly, we examined the nitric oxide (NO) production in macrophage cell line in order to evaluate the anti-inflammatory effect. The expression levels of inflammation related genes including IL-1 beta, IL-6, INOS, and TNF-alpha were examined via a real-time quantitative PCR. Croton oil-induced hemorrhagic animal model was used to test the in vivo efficacy against hemorrhoids. The rectal tissues were weighed and the inflammatory proteins were measured to confirm the anti-inflammatory effects. Results : JG and CS have a statistically significant effect on inhibition of NO production and on the reduction of inflammatory gene expression such as IL-1 beta, IL-6, INOS, and TNF-alpha. The synergistic effects of co-treatment of JG and CS were found out in the IL-6 gene expression. The in vivo study using croton oil-induced hemorrhoid model in rat was performed to check the co-treatment effects. As a result, the co-treatment reduced the inflammation of the rectal tissue and decrease the inflammation related protein productions including ICAM1, MMP2 and MMP9. Conclusions : These results suggest that JG and CS co-treatment demonstrated anti-inflammatory effects in croton oil-induced hemorrhoid model in rat.

• 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.

• Nutrition Research and Practice
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• v.8 no.3
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• pp.284-291
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• 2014

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the effects of exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging model rats with diet-induced atherosclerosis. MATERIALS/METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF-EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical and immunohistochemical analyses. REULTS: The EX and KRG supplementation significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group showed a decreased plasma CRP and increase plasma NO activities compared to AHF group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-, ${\alpha}$, IL-6, COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta. CONCLUSION: These results suggest that EX alone, KRG alone, and combined treatment of EX and KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis, possibly acting via the decreased of CRP and pro-inflammation proteins and the increased NO and eNOS.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.9-23
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• 2009

Objectives : Asthma is a chronic inflammatory disorder of the airways by many cells such as mast cells, Th2 lymphocytes and eosinophile. The present study was aimed to evaluate the effects of Salviae miltiorrhizae (SM) on T cell cytokine production, mast cells. and eosinophils, Methods : We screened 13 herbs to find compounds with potential to control Th cytokine production. using concanavalin A (con A)-activated splenocyte cultures. Con A-activated $IFN-\gamma$ and IL-4 levels in supernatants of splenocyte cultures. Bone marrow derived mast cells (BMMC) were incubated with SM and then the expressions of membrane proteins of BMMC were analyzed by fluorescence activated cell sorter (FACS). BALB/c mice sensitized to ovalbumin (OVA) were challenged with aerosolized OVA for 6 weeks. During the last weeks some mice were treated with SM. Then eosinophils in bronchoalveolar lavage fluid (BALf) were counted and pathologic changes of lung tissue were observed with hematoxylin-eosin stain. Results : SM increased $IFN-\gamma$ level on splenocyte culture significantly. but had no significant effects on expressions of ICAM-1, CD62L, integrin $a_4$. c-kit, IL-3 receptors. CD11a, or IgE receptors of BMMC. SM treatment significantly inhibited eosinophil infiltrates in BALf and peribronchial lung inflammation. Conculusions : The present data suggested that SM may have an effect on Th cytokine secretion and eosinophils associated with asthma responses. Therefore SM might be of therapeutic value in treating asthma.

• Asian Pacific Journal of Cancer Prevention
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• v.18 no.11
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• pp.2919-2923
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• 2017

Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant and anti-inflammatory actions have been reported to have anti-cancer effects. Here, we investigated whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in human lung cancer A549 cells, which are critically involved in cancer metastasis. Methods: We used anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. We have performed cell proliferation assays, cell invasion assay, gelatin zymography, wound healing assay and western blotting to examine whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not inhibit cancer cell proliferation on A549 cells. Also, AIMs suppressed cancer migration, and invasion by supressing MMP-2 and MMP-9 expression. The Immuno-blotting results also revealed that AIMs suppressed the proteins involved in cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2, MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion and angiogenesis (ICAM-1, VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit cancer proliferation, cancer migration, and invasion that is involve in cancer-metastasis. This study provides evidence that AIMs might have anti-cancer effects on human lung cancer.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.41-51
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• 2021

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson's trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.113-119
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• 2009

Benzo(a)pyrene (BaP) is a persistent environmental contaminant and is present in tobacco smoke. BaP is considered a major contributor of cardiovascular disease. While the activation of endothelial cells by stimuli including tobacco smoke and air pollution contributes importantly to cardiovascular disease, the nature of BaP's mechanism is unclear. In this study, gene expression profiles were investigated in BaPtreated human umbilical vein endothelial cells (HUVECs). Various atherosclerosis related genes could be up- and down-regulated more than 2-fold by BaP, and mRNA levels of atherosclerosis related genes encoding apolipoproteinC III, TLR 2, ICAM 1 and exportin 4 were significantly increased by BaP. Our data suggest that BaP-mediated changes in gene expression contribute to the progression of cardiovascular disease.