• Radiation Oncology Journal
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• v.23 no.1
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• pp.51-60
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• 2005

Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

• Herbal Formula Science
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• v.22 no.2
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• pp.63-76
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• 2014

Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) on obesity in a high fat diet-fed obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into four groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and DF-a and DF-b groups given a high fat diet with DF-a (80 mg/kg), and DF-b (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : 1. Body weight gain and fat mass were significantly decreased in DF-a and DF-b groups compared with control. The extent of decreases was eminent in DF-a group. 2. Feeding efficiency ratio and circulating leptin concentration were significantly decreased in DF-a and DF-b groups compared with control, whereas circulating adiponectin concentration was increased in DF-a and DF-b groups compared with control. 3. Consistent with their effects on body weight gain and fat mass, circulating concentrations of triglyceride, glucose and insulin were decreased in DF-a and DF-b groups compared with control. 4. The size of adipocytes were decreased by DF-a and DF-b compared with control, whereas the adipocyte number per unit area was increased by them, suggesting that DF-a and DF-b decreased the number of large adipocytes. 5. Consistent with their effects on body weight gain, liver fibrosis was reduced in DF-a and DF-b groups compared with control. Conclusions : In conclusion, these results suggest that DF-a and DF-b not only decrease feeding efficiency ratio, plasma leptin concentration, and blood anti-obesity biomarkers, but also reduce fat mass, contributing to the improvement of obesity. DF-a and DF-b also inhibit liver fibrosis. In addition, these effects were similar between Pakistani Ephedra herba and Chinese Ephedra herba-containing Gangjihwan.

• Herbal Formula Science
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• v.22 no.2
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• pp.105-120
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• 2014

Objectives : This study was investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on obesity in a high fat diet-fed obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into four groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and DF and DF+GSH groups given a high fat diet with DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : 1. Body weight gain and fat mass were significantly decreased in DF and DF+GSH groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Feeding efficiency ratio and circulating concentration of leptin were decreased in DF and DF+GSH groups compared with control. These decreases were significant in DF+GSH group. 3. Consistent with their effects on body weight gain and fat mass, circulating concentrations of triglyceride, glucose and insulin were decreased in DF and DF+GSH groups compared with control. 4. The size of adipocytes was decreased by DF and DF+GSH compared with control, whereas the adipocyte number per unit area was increased by them, suggesting that DF and DF+GSH decreased the number of large adipocytes. 5. Consistent with their effects on body weight gain, liver fibrosis was also improved in DF and DF+GSH groups compared with control. Conclusions : In conclusion, these results suggest that DF and DF+GSH groups decrease feeding efficiency ratio, plasma leptin concentration, blood anti-obesity biomarkers and fat mass, improves body weight gain contributing to the inhibition of liver fibrosis. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.501-509
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• 2012

The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. In our previous study, hog millet (HM, $Panicum$ $miliaceum$ L.) water extract showed the highest anti-lipogenic activity among nine cereal types in 3T3-L1 cells. In this study, the effect of hog millet water extract on hepatic steatosis and lipid metabolism in mice fed a high fat diet was investigated. Mice were fed a normal-fat diet (ND), high-fat diet (HFD) or HFD containing 1% or 2% (w/w) HM for 7 weeks. Body weight and food intake were monitored during the study period. Insulin resistance by homeostasis model assessment (HOMA-IR), fasting lipid profile, hepatic fatty acid metabolism-related gene expression determined, and intraperitoneal glucose tolerance test (IGTT) were performed at the study's end. The results indicated that 1% and 2% HM diets effectively decreased liver weights, blood TG and T-cholesterol levels (p<0.05), while the HDL-cholesterol level was increased (p<0.05) compared to HFD-induced steatotsis mice. Hepatic lipogenic-related gene ($PPAR{\alpha}$, L-FABP, and SCD1) expressions decreased, whereas lipolysis- related gene (CPT1) expression increased in animals fed the 2% PME diet (p<0.05). In addition, mice fed 1% or 2% HM diet had markedly decreased IGTT and HOMA-IR, compared to the those of the HFD-induced hepatic steatosis control group (p<0.05). These results indicated that HM inhibited hepatic lipid accumulation by regulating fatty acid metabolism, and suggested that HM is useful in the chemoprevention or treatment of high fat-induced hepatic steatosis and hepatic steatosis-related disorders including hyperlipidemia, glucose sensitivity, and insulin resistance.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.39 no.3
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• pp.177-186
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• 2013

Skin dermal fibroblast is the major collagen-producing cell type in human skin. As aging process continues in human skin, collagen production is reduced and fragmentation is increased, which is initiated by matrix metalloproteinase-1 (MMP-1). This imbalance of collagen homeostasis impairs the structure and function of dermal collagenous extracellular matrix (ECM), thereby promoting skin aging. Cysteine-rich protein 61 (CCN1), a member of the CCN family, negatively regulates collagen homeostasis in primary human skin dermal fibroblast cells. It is known in aging fibroblast cells that elevated CCN1 expression substantially reduces type I procollagen and concurrently increases MMP-1, which initiates fibrillar collagen degradation. And proliferation rate of aging fibroblast cells is reduced compared to the pre-aging fibroblast cells. In this study, we confirmed that the replicative senescence dermal fibroblast cells increased the expression levels of MMP-1 and decreased the production of type I procollagen. Our results also showed that the replicative senescence dermal fibroblast cells increased in the expression of CCN1 and decreased in the proliferation rate. Hydrolyzed Ulva pertusa extracts are the materials to improve photo-aging by reducing the expression of MMP-1 that was increased by ultraviolet and by promoting the synthesis of new collagen from fibroblast cells. In this study, we also investigated the hydrolyzed U. pertusa extract to see whether it inhibits CCN1 protein expression in the senescence fibroblasts. Results showed that the hydrolyzed U. pertusa extract inhibited the expression of MMP-1 and increased the production of type I procollagen in the aging skin fibroblast cells cultured. In addition, the proteins that regulate collagen homeostasis CCN1 expression were greatly reduced. The hydrolyzed U. pertusa extract increased the proliferation rate of the aging fibroblast cells. These results suggest that replicative senescent fibroblast cells may be used in the study of cosmetic ingredients as a model of the natural aging. In conclusion, the hydrolyzed U. pertusa extract can be used in anti-wrinkle functional cosmetic material to improve the natural aging skin care as well as photo-aging.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1544-1551
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• 2016

Various types of fermented soybean foods are consumed in various Asian countries, including China, Indonesia, Japan, Korea, and Vietnam. Cheonggukjang is a Korean whole soybean paste fermented by Bacillus subtilis and regarded as a healthy food. The objective of this study was to investigate the Ca-bioavailability and anti-osteoporotic effects of cheonggukjang (CGJ) containing high poly-gamma glutamate (PGA) contents in an animal model. Blood samples were collected from the jugular vein at 0, 0.5, 1, 2, 3, 4, and 5 h after a single oral dose in male rats. Ca-bioavailability in CGJ containing high PGA contents was approximately 3~5 times higher than that of natural CGJ. Female rats were either sham-operated (sham; n=5) or surgically ovariectomized (OVX; five animals per group) and then administered to OVX control, raloxifene hydrochloride (RLX) 1 mg/kg/d, or CGJ containing high contents of PGA (20 and 200 mg/kg/d) for 12 weeks. Serum osteocalcin concentration was significantly lower in the CGJ 200 mg/kg/d group compared with the OVX control group. Serum progesterone concentration was significantly higher in the CGJ 200 mg/kg/d group compared with the OVX control group. Reduction grade of the trabecular bone decreased in the RLX 1 and CGJ 200 mg/kg/d group compared with that of the OVX control group. In conclusion, CGJ 200 mg/kg/d may have inhibitory effects on osteoporosis in OVX rats, and Ca-bioavailability was improved in CGJ containing high PGA contents.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.26-35
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• 2006

Background: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-${\kappa}B$ and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. Materials and Methods: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-${\kappa}B$ $cis$-elements. C57BL/6 NF-${\kappa}B^{EGFP}$ mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-${\kappa}B$ activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. Results: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-${\kappa}B$ activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. Conclusions: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.45 no.2
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• pp.175-184
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• 2019

The epidermal growth factor (EGF) has a intrinsic function of inducing growth and proliferation of cells through interacting with cell membrane receptors in human epidermis and dermis layer. These functions of EGF are used as a main ingredient for wound healing medicines and anti-aging cosmetics. As a cosmetic ingredient, the EGF has a problem in exhibiting its natural efficacy due to the lack of the ability to penetrate through the stratum corneum, which is known as the skin barrier. In this study, a recombinant human epidermal growth factor ($MTD_{151}-EGF$) fused with the macromolecule transduction domain $(MTD)_{151}$ with the skin penetration ability was developed to improve the skin penetration efficiency of the EGF. Expression of $MTD_{151}-EGF$ was performed in E. coli transformed with a vector encoding the $MTD_{151}-EGF$ gene and then purified. The purified $MTD_{151}-EGF$ was evaluated using cell proliferation assay, cytotoxicity test and skin penetration test by franz diffusion cell assay and artificial skin. Cell proliferation activity of $MTD_{151}-EGF$ purified to high purity of 99% or above was equivalent to the EGF or better, and cytotoxicity was not observed. In addition, the $MTD_{151}-EGF$ showed an excellent penetration efficiency compared to the EGF in the skin penetration test with EGF and $MTD_{151}-EGF$ labeled by FITC in an artificial skin penetration model. Based on the quantitative analysis of the penetrating substance using franz diffusion cell assay, the amount of penetration was about 16 times more than that of EGF. These results can be regarded as an effective alternative to improve the existing physical transdermal penetration method related to the use of various active ingredients for cosmetics.

• Journal of Life Science
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• v.29 no.5
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• pp.570-579
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• 2019

Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

• Journal of Food Hygiene and Safety
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• v.36 no.6
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• pp.528-536
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• 2021

The purpose of the study was to investigate the content of sinigrin, an index component, in Brassica juncea extract and to evaluate the differentiation of lipocytes, inhibition of production of reactive oxygen species (ROS) and reduction of protein production by lipogenic factors (PPARγ, C/EBPα, aP2) in the processing of Brassica juncea extract and sinigrin in 3T3-L1 preadipocytes which induces Bisphenol A (BPA), an endocrine disrupting environmental hormone. From the investigation, the content of sinigrin in Brassica juncea extract, measured by HPLC, is found to be 21.27±0.2 mg/g. The XTT assay result on BPA-derived 3T3-L1 adipocytes shows there is no cytotoxicity found from 180 µM of sinigrin and 300 ㎍/mL of Brassica juncea extract. Moreover, both intracellular lipid accumulation and ROS production during differentiation of lipocyte are significantly reduced in cells processed with Brassica juncea extract and sinigrin. Lastly, it was also found that the production of transcription factors of lipocyte differentiation, PPARγ, C/EBPα and aP2, were found to be suppressed by the application of Brassica juncea extract and sinigrin. Such results reveals that Brassica juncea is effective in not only suppressing lipid accumulation in the environmental hormone bisphenol A-derived lipocyte, but also in reducing the ROS. The sinigrin-containing Brassica juncea is highly expected to be used in natural functional supplements that prevents the lipid metabolism disorders caused by BPA. There are necessities for additional clinical research and follow-up studies on the in vivo model to verify the relevant mechanisms.