• Journal of Periodontal and Implant Science
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• v.46 no.2
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• pp.84-95
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• 2016

Purpose: The objective of this study was to investigate the effect of a dietary flavonoid, kaempferol, which has been shown to possess antiallergic, anti-inflammatory, anticarcinogenic, and antioxidant activities on the periodontium by histomorphometric analysis and on gingival tissue matrix metalloproteinase-1 (MMP-1), MMP-8, and tissue inhibitor of metalloproteinase-2 (TIMP-2) by biochemical analysis of rats after experimental periodontitis induction. Methods: Sixty Wistar rats were randomly divided into six groups of ten rats each, and silk ligatures were placed around the cervical area of the mandibular first molars for 15 days, except in the healthy control rats. In the experimental periodontitis groups, systemic kaempferol (10 mg/kg/2d) and saline were administered by oral gavage at two different periods (with and without the presence of dental biofilm) to all rats except for the ten non-medicated rats. Alveolar bone area, alveolar bone level, and attachment level were determined by histomorphometric analysis, and gingival tissue levels of MMP-1, MMP-8, and TIMP-2 were detected by biochemical analysis. Results: Significantly greater bone area and significantly less alveolar bone and attachment loss were observed in the kaempferol application groups compared to the control groups (P<0.05). In addition, gingival tissue MMP-1 and -8 levels were significantly lower in the kaempferol application groups compared to the control groups and the periodontitis group (P<0.001). There were no statistically significant differences in TIMP-2 levels between the kaempferol and saline application groups (P>0.05). Conclusions: Kaempferol application may be useful in decreasing alveolar bone resorption, attachment loss, and MMP-1 and -8 production in experimental periodontitis.

• CELLMED
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• v.2 no.3
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• pp.27.1-27.6
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• 2012

Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and $I{\kappa}B$ kinase-beta (IKK-${\beta}$) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-${\beta}$ for the first time. When HRG was used in combination with recombinant interferon-${\gamma}$ (rIFN-${\gamma}$), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-${\gamma}$ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). In addition, the treatment of peritoneal macrophages with rIFN-${\gamma}$ plus HRG caused significant increases in tumor necrosis factor (TNF)-${\alpha}$ mRNA expression and production. Because NO and TNF-${\alpha}$ play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-${\kappa}B$. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-${\alpha}$ from rIFN-${\gamma}$-primed macrophages and suggest that Rip2/IKK-${\beta}$ plays a critical role in mediating these immune regulatory effects of HRG.

• BMB Reports
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• v.32 no.3
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• pp.259-265
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• 1999

This study was designed to examine the anticarcinogenic effect of dietary supplementation with garlic powder on rat hepatocarcinogenesis. All rats were initiated by a single dose (200 mg/body weight) intraperitoneal injection of diethylnitrosamine (DEN), and three weeks later, subjected to two-thirds partial hepatectomy. Two weeks after initiation, four groups of rats were given experimental diets supplemented with 0 (control group), 0.5, 2.0, or 5.0% garlic powder for 6 weeks. Rats were sacrificed at eight weeks after initiation. The induction of placental glutathione S-transferase (GST-P) positive foci was significantly inhibited almost equally in all three groups fed garlic diets. Glucose 6-phosphatase (G6Pase) activity was increased in rats fed 0.5% and 2.0% garlic powder, and was negatively correlated with the number and area of GST-P positive foci. Thiobarbituric acid reactive substance (TBARS) contents were decreased in rats fed 2.0% and 5.0% garlic powder. Only 5.0% garlic powder supplementation significantly increased the glutathione content and the glutathione S-transferase activity, compared to the control group. Therefore, all levels of garlic powder, 0.5% to 5.0%, exerted an anti promotional effect during hepatocarcinogenesis. Dietary supplementation with garlic powder seemed to maintain microsomal membrane integrity by increasing G6Pase activities. Glutathione-dependent detoxifying enzymes did not seem to contribute to this protective effect directly. The present study suggests that garlic powder is effective in inhibiting the induction of GST-P positive foci, possibly by stabilizing the hepatic microsomal membrane.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.2
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• pp.193-197
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• 1997

Elevation of the activities of phase 2 enzymes such as quinone reductase(QR) provides protection against several types of neoplasia. In this study, we performed partial purification of QR inducer(s) from roasted and defatted perilla meal by solvent fractionation and thin layer chromatography. Cellular QR induction was most notable in chloroform fraction of roasted perilla extract, compared with other solvent fractions. QR inducer(s) was partially purified by TLC, with 0.8 of $R_f$ value in n-butanol : n-propanol : 2N-ammonium hydroxide(10 : 60 : 30). AHH-inducing activity in TLC fractions isolated from methanol extracts of roasted perilla comigrated with QR-inducing fraction, suggesting that QR and AHH are induced by the same compound. TLC fractions shown strong QR-inducing activity also had a potent antioxidative activity, suggesting that cellular QR enzyme is induced by antioxidant(s) present in roasted perilla.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.339-339
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• 1994

It has been reported that Indole-3-carbinol (I3C), a naturally occurring compound In cruclferous vegetables, exerts anticarcinogenic activity In several organs In rodents. The modifying effects of I3C were therefore assessed uging a rat multi-organ carcinogenesis model. A total of 100 male Sprague-Dawley rats were divided Into 3 groups. Animals of groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., i.p.), N-methylnitrosourea (NNU; 20 mg/kg b.w., 4 times for 2 weeks, i.p), and dihydroxy-di-N-propylnitrosauine (DHPN; 0.1% In d.w. for 2 weeks) for 4 weeks (DMD treatment). Animals of groups 1 and 3 were given the diet of 0.25% I3C for 20 weeks after DMD initiation and then were given basal diet for 28 weeks. All animals were sacrificed at week 24 and 52, respectively. I3C has been clearly demonstrated promoting effects on the development of glutathione S-transferase placental form (GST-P) positive hepatic foci at 24 weeks of the experiment. And I3C also exerted promoting potential In the hepatocellular adenoma (4/14; 29%) and the adenoma (7/14; 50%) of the thyroid gland at 52 weeks of the experiment. Therefore, I3C may promote hepatocarcinogenesis and thyroid tumorigenesis in the rat multi-organ carcinogenesis model.

• BMB Reports
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• v.34 no.3
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• pp.189-193
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• 2001

Curcumin a yellow pigment from Curcuma Tonga, has been known to possess antioxidative and anticarcinogenic properties, as well as to induce apoptosis in some cancer cells. There have been, however, several contradictory reports that hypothesized curcumin (a hydrophobic molecule) can bind a membrane Gpid bilayer and induce nonspecific cytotoxicity in some cell lines. Why curcumin shows these contradictory effects is unknown. In A-431 cells, growth inhibition by curcumin is due mostly to the specific inhibition of the intrinsic tyrosine kinase activity of the epidermal growth factor receptor, as reported earlier by Korutla et al. Thus, we assumed that the cell death of A-431 by curcumin might be due to the specific induction of apoptosis. In this paper we clearly show that curcumin induces apoptosis in A-431 cells. The cureumin-induced cell death of A-431 exhibited various apoptotic features, including DNA fragmentation and nuclear condensation. Furthermore, the curcumin-induced apoptosis of A-431 cells involved activation of caspase-3-like cysteine protease. Involvement of caspase-3 was further confirmed by using a caspase-3 specific inhibitor, DEVD-CHO. In another study, decreased nitric oxide (NO) production was also shown in A-431 cells treated with curcumin, which seems to be the result of the inhibition of the iNOS expression by curcumin, as in other cell lines. However, 24 h after treatment of curcumin there was increased NO production in A-431 cells. This observation has not yet been clearly explained. We assumed that the increased NO production may be related to denitrosylation of the enzyme catalytic site in caspase-3 when activated. Taken together, this study shows that the cell death of A-431 by curcumin is due to the induction of apoptosis, which involves caspase-3 activation.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.364-372
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• 2005

This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.335-343
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• 2005

Rodent models have been used to study the anticarcinogenic properties of the soy isoflavones, particularly genistein, but there is little information regarding the pharmacokinetics of the absorption and excretion of genistein. In this study, rats were given a single oral dose of genistein (20 mg/kg body wt) or an equivalent dose as Myougjoonamul-kong and Myoungjoonamul soy sprouts. Concentrations of genistein were measured in plasma, urine and feces at intervals up to 48hr after dosing. Maximum peak of plasma genistein concentration is 8 hr after dosing, and its concentration is 13.2, 7.4mol/L in soy and soy sprout-treated rats, respectively. In pure genistein treated rats, maximum peak of plasma genistein concentration is 2hr after dosing (5.7 mol/L). The percentage of dose recovered in urine over 48hr was not different between groups ($21.2\%$ soy treated; $18.2\%$ soy sprout treated; $16.1\%$ pure genistein treated). There were no significant differences between groups in the recovery of genistein in feces ($19.5\%,\;7.5\%\;and\;15.7\%$ of doses, respectively). $6.9\%\;and\;6.07\%$ of the daidzein from the soy and soy sprout treated was recovered in the feces.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.280-286
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• 2003

Conjugated linoleic acid (CLA) consists of several geometric isomers of linoleic acid. CLA is found in foods derived from ruminants and exhibits strong anticarcinogenic effects in a variety of animal models. Matrix metalloproteinases (MMPs) play a key role in cancer progression. Specifically, MMP-2 and -9, which hydrolyze the basal membrane type IV collagen, are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. However, the effects of CLA on cancer cell motility and MMP expression and activity are not currently well known. Therefore, the present study examined whether CLA reduces the activity of MMP and cell motility in SW480 and SW620 cells, the human colon cancer cell lines. Gelatin zymography and Western blot analysis revealed that phorbol 12-myristate 13-acetate (PMA) induced the activity and protein expression of Mr 92,000 MMP-9 in both cell lines. To examine whether CLA inhibits the MMP activity, cells were incubated with 100 ngfmL PMA in the presence of various concentrations of CLA. PMA-induced MMP-9 activity was decreased by 20 $\mu$ M CLA in SW480 cells, and by 10 $\mu$ M and 20 $\mu$ M CLA in SW620 cells. Results from the Hoyden chamber assay showed that cell motility was increased by PMA and that PMA-induced cell motility was significantly decreased by 20 $\mu$ M CLA in SW480 cells. These results indicate that CLA may reduce the motility and MMP activity in human colon cancer cells.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.270-279
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• 2003

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid (LA) and exhibits anticarcinogenic activity in a variety of animal models. We have previously observed that CLA inhibited the growth of Caco-2 cells, a human colon adenocarcinoma cell line. The present study was performed to determine whether the growth inhibitory effect of CLA is related to change in secretion of IGF- II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate Caco-2 cell proliferation by an autocrine mechanism. Cells were incubated in serum-free medium with various concentrations of CLA or linoleic acid (LA). Immunoblot analysis of 24-hours, serum-free, conditioned medium using a monoclonal anti-IGF-IIantibody revealed that Caco-2 cells secreted both mature 6,500 Mr and higher Mr forms of pro IGF-II. The levels of pro IGF-II and mature IGF-IIwere decreased by 43 $\pm$ 2% and 53 $\pm$ 6%, respectively by treatment with 50 $\mu$ M CLA. LA slightly increased pro IGF- II levels. Results from Northern blot analysis showed that CLA decreased IGF-II mRNA levels at 50 $\mu$ M concentration suggesting that CLA regulation of IGF-II protein expression occurs partly at the transcriptional level. Ligand blot analysis of conditioned media using 1251-IGF-II revealed that CLA slightly decreased IGFBP-2 levels and increased IGFBP-4 levels. We confirmed our previous results that CLA inhibited cell growth in a dose-dependent manner but LA slightly increased cell growth. Exogenous IGF-II mitigated the growth inhibitory effect of CLA. These results indicate that the growth inhibitory effect of CLA may be at least in part mediated by decreasing IGF-II and IGFBP-2 secretion and increasing IGFBP-4 secretion in Caco-2 cells.