• Asian-Australasian Journal of Animal Sciences
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• v.21 no.6
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• pp.853-860
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• 2008

This experiment was conducted to study the effects of chromium (Cr), dietary crude protein (CP) level and potential interactions between these two factors on growth rate and carcass response, insulin activity and lipid metabolism in lambs. Forty-eight, 9-week-old weaned lambs (Dorper$\times$Small-tail Han sheep, mean initial body weight = $22.96kg{\pm}2.60kg$) were used in a $2{\times}3$ factorial arrangement of supplemental Cr (0 ppb, Cr0; 400 ppb, Cr1; or 800 ppb, Cr2 from chromium yeast) and CP levels (157 g/d to 171 g/d for each animal, LP; or 189 g/d to 209 g/d for each animal, HP). Growth data and blood samples were collected at the beginning and end of the feed trial, after which the lambs were killed. Both Cr additive groups and the HP group increased final weight and average daily gain, especially the Cr1 and HP group (p<0.01). HP increased pelvic fat weight (p<0.05), fat thickness of the 10th rib (p<0.05), longissimus muscle area (p<0.01) and rate of deposition of intramuscular fat (p<0.01). Supplemental Cr decreased the rate of deposition of intramuscular fat (p<0.05). Fasting insulin level and the ratio of insulin to glucose were lower with Cr1 than other groups, but with no significant difference. Glucose concentration was not affected by any treatment. Nonesterified fatty acids increased in the Cr1 (p<0.05) and HP (p<0.05) conditions and there was a significant $Cr{\times}CP$ interaction (p<0.05). Cr1 decreased triglycerides (p<0.05) and total cholesterol (p = 0.151) and HP increased high-density lipoprotein cholesterol (p<0.05). Cr1 decreased lipoprotein lipase activity in subcutaneous adipose tissue (aLPL, p<0.05) and the ratio of aLPL to lipoprotein lipase activity in skeletal muscle (mLPL, p = 0.079). mLPL and hepatic lipase (hHL) were not affected by any treatment. In the present study, Cr had limited effects on growth rate and carcass response, whereas Cr and CP had some notable effects on plasma metabolites and enzyme activities. Cr has a potential effect on energy modulation between lipid and muscle tissue. In addition, few $Cr{\times}CP$ interactions were observed.

• Food Science and Preservation
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• v.19 no.3
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• pp.455-461
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• 2012

Obesity, a strong risk factor for the development of chronic diseases, is characterized by an increase in the number and size of adipocytes differentiated from precursor cells, preadipocytes. Recent research suggests that increased reactive oxygen species (ROS) production in 3T3-L1 adipocyte facilitates adipocyte differentiation and fat accumulation. This study was to investigate whether reduced ROS production by Sargassum micracanthum extract (SME) could protect the development of obesity through inhibition of adipogenesis. 3T3-L1 preadipocytes were treated SME for up to 8 days following standard induction of differentiation. The extent of differentiation reflected by amount of lipid accumulation and ROS production was determined by Oil red O staining and nitroblue tetrazolium (NBT) assay. Treatment of SME significantly inhibited ROS production and adipocyte differentiation that is depend on down regulation of NADPH oxidase 4 (NOX4), a major ROS generator, and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha ($C/EBP{\alpha}$), a key adipogenic transcription factor. These results indicate that SME can inhibit adipogenesis through a reduced ROS level that involves down-regulation of NOX4 expression or via modulation of adipogenic transcription factor.

• Journal of Nutrition and Health
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• v.55 no.6
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• pp.617-629
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• 2022

Purpose: Osteoporosis is characterized by structural deterioration of the bone tissue because of the loss of osteoblastic activity or the increase in osteoclastic activity, resulting in bone fragility and an increased risk of fractures. Hederagenin (Hed) is a pentacyclic triterpenoid saponin isolated from Dipsaci Radix, the dried root of Dipsacus asper Wall. Dipsaci Radix has been used in Korean herbal medicine to treat bone fractures. In this study, we attempted to demonstrate the potential anti-osteoporotic effect of Hed by examining its effect on osteoblast differentiation in MC3T3-E1 cells. Methods: Osteoblastic MC3T3-E1 cells were cultured in 0, 1, and 10 ㎍/mL Hed for 3 and 7 days. The activity of alkaline phosphatase (ALP), bone nodule formation and level of expression of bone-related genes and proteins were measured in MC3T3-E1 cells exposed to Hed. The western blot test was used to detect the activation of the bone morphogenetic protein-2 (BMP2)/ Suppressor of Mothers against Decapentaplegic (SMAD)1 pathway. Results: Hed significantly increased the proliferation of MC3T3-E1 cells. Intracellular ALP activity was significantly increased in the 1 ㎍/mL Hed-treated group. Hed significantly increased the concentration of calcified nodules. Furthermore, Hed significantly upregulated the expression of genes and proteins associated with osteoblast proliferation and differentiation, such as Runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN), and type I procollagen (ProCOL1). Induction of osteoblast differentiation by Hed was associated with increased BMP2. In addition, Hed induced osteoblast differentiation by increasing the activity of SMAD1/5/8. These results suggest that Hed has the potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells via the modulation of the BMP2/SMAD1 pathway. Conclusion: The results presented in this study indicate that Hed isolated from Dipsaci Radix has the potential to be developed as a healthcare food and functional material possessing anti-osteoporosis effects.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4539-4543
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• 2014

Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.

• The Korea Journal of Herbology
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• v.25 no.4
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• pp.103-112
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• 2010

Objective : The aim of this study was to determine whether methanol extract of Do-Ki-Tang (DKT) inhibit free radical generation and production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods : Cytotoxic activity of extract on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The expression level of inflammatory response-related proteins was confirmed by western blot. The production of proinflammatory cytokines was measured by ELISA. Results : Our results indicated that DKT scavenged DPPH radical and nitric oxide in vitro. Moreover, DKT significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 formation in macrophages. Furthermore, DKT treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$ and MAPKs. Conclusion : Our data suggest that the anti-inflammatory effect of DKT is mediated through down-modulation of pro-inflammatory mediators and cytokines by blocking the signaling pathways of NF-${\kappa}B$ and MAPKs. These inhibitory effects by DKT represent a potential therapeutic approach to the treatment of inflammatory diseases.

• Journal of Korean Neurosurgical Society
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• v.38 no.5
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• pp.366-374
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• 2005

Objective : Nitric oxide[NO] is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. Methods : U87MG and U373MG cells were treated with the NO donors sodium nitroprusside[SNP] and S-nitroso-N-acetylpenicillamine[SNAP], alone or in combination with the anticancer drugs 1,3-bis[2-chloroethyl]-1-nitrosourea[BCNU] and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. Results : NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. Conclusion : BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.510-516
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• 2016

Isoegomaketone (IK) was isolated from Perilla frutescens, which has been widely used as a food in Asian cuisine, and evaluated for its biological activity. We have already confirmed that IK induced the HO-1 expression via Nrf2 activation in RAW264.7 cells. In this study, we investigated the effect of IK on the mechanism of HO-1 expression. IK upregulated HO-1 mRNA and protein expression in a dose dependent manner. The level of HO-1 mRNA peaked at 4 h after $15{\mu}M$ IK treatment. To investigate the mechanisms of HO-1 expression modulation by IK, we used pharmacological inhibitors for the protein kinase C (PKC) family, PI3K, and p38 MAPK. IK-induced HO-1 mRNA expression was only suppressed by SB203580, a specific inhibitor of p38 MAPK. ROS scavengers (N-acetyl-L-cysteine, NAC, and glutathione, GSH) also blocked the IK-induced ROS production and HO-1 expression. Furthermore, both NAC and SB203580 suppressed the IK-induced Nrf2 activation. In addition, ROS scavengers suppressed other oxidative enzymes such as catalase (CAT), glutathione S-transferase (GST), and NADH quinone oxidoreductase (NQO-1) in IK-treated RAW264.7 cells. Taken together, it can be concluded that IK induced the HO-1 expression through the ROS/p38 MAPK/Nrf2 pathway in RAW264.7 cells.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.133-140
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• 2009

Caveolin may be a molecular target for modulation of aging process in cochlear hair cells and have association with oxotoxicity. First we investigated the basal expression of caveolin-1, caveolin-2, caveolin-3, nitric oxide synthase, and superoxide dismutase in UB/OC-1 cochlear hair cell line. By using a RNA interference technique, we investigated whether down-regulation of caveolin influenced telomerase activity and reactive oxygen species (ROS) production in cochlear hair cells. In addition, cisplatin and gentamycin, known ototoxic drugs, were administered to the cochlear cells to determine their impact on caveolin expression. Further attempts at elucidating cellular aging mechanism with caveolin and ototoxic drugs were carried out. The main discoveries were the presence of caveolin-1 in UB/OC-1 cells and that down-regulation of caveolin-1 reduced protein kinase A activity. Telomerase was activated by caveolin down-regulation and caveolin down-regulation inhibited oxidative stress at the mitochondrial level. When cisplatin and gentamycin were administered to the cochlear hair cells during a caveolin expression state, a decrease in telomerase activity and increase ROS activity was observed. Caveolin-1 may modulate the senescent mechanisms in cochlear cells. An increase in caveolin-1 levels can lead to ROS production in the mitochondria which may cause ototoxicity.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.101-118
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• 2011

Herbal medicine has a high body absorption rate when it ferments. Biological and clinical research on the fermented herb gradually increases because it has effective materials for the treatment of a disease and it is a little bitter. In this study, we investigated the effect of fermented Baedokhwanbalhyobang (BDHBH) on attenuation of the development of atopic dermatitis in NC/Nga mice by evaluating the cytokine level in serum, the mRNA expression of cytokine and histological alteration of the skin, and the skin severity. We have come to the following conclusion. BDHBH led to a significant decrease in the skin severity score (63.1%) as compared to the control group. CD4+/CD45+, CD4+, B220+/CD23+, and CD11b+/Gr-1+cells of peripheral mononuclear cells (PBMCs) in the BDHBH-treated group were decreased to 6.7%, 31.1%, 22.4%, 36.6%, respectively. CD3+and CD11b+/Gr-1+immune cells in dorsal skin of the BDHBH-treated group were decreased to 52.9% and 28.0%. The levels of IL-5 and IL-13 in serum of the BDHBH-treated group were inhibited to 18.8% and 5.1%. The mRNA expressions of IL-5 and IL-13 in dorsal skin were also decreased to 30.6% and 27.8% after the treatment of BDHBH. BDHBH inhibited the proliferation and differentiation of eosinophils. In histological examination, BDHBH decreased the thickness of epidermis and dermis, and infilatration of mast cells as compared to the control group. These results indicate that BDHBH inhibits the pathogenic development of atopic dermatitis in NC/Nga mice. These results may indicate that BDHBH attenuates the development of atopic dermatitis-like lesions by lowering immune cells and inflammatory cytokine levels, and that it is valuable in drug development for the treatment of atopic dermatitis. Further experiments on the components of BDHBH will be needed to better understand the effect of a fermented herb as compared to a herb.

• Korean Journal of Acupuncture
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• v.33 no.4
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• pp.204-212
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• 2016

Objectives : The aim of the study is to investigate the effects of moxibustion on the pain behavior and expression of TRPM8 in the dorsal root ganglion(DRG) in the rat model of ambient cold(AC) exposed osteoarthritis(OA). Methods : OA was induced by the injection of $50{\mu}l$ of 2% monosodium iodoacetate(MIA) into the knee joint cavity. To examine the level of pain, weight bearing forces(WBFs) of affected limb was measured. For the AC exposure, the animals were housed in 6 h/day at $4^{\circ}C$ for 14 days after MIA injection. Moxibustion treatment was performed at EX-LE4 and EX-LE5 with 5 cons(1, 7 or 10 mg) per day for 13 days from 5 days after MIA injection. The expressions of TRPM8 in DRG were measured by western blotting analysis. Results : The WBFs of MIA-AC group were decreased significantly compared to MIA group at 2, 3, 6, 7, 8 and 9 days after arthritis induction. After the first 6 h-AC exposure, expressions of TRPM8 in MIA-AC group were increased significantly compared to those of naive group. After moxibustion treatment, only the WBFs of 7 mg treated group were restored significantly. Moreover, the over-expressions of TRPM8 were attenuated by the moxibustion treatment in AC exposed rats. Conclusions : The data suggest that AC can increase arthritic knee pain via up-regulated TRPM8 and moxibustion treatment improve the arthritic pain via modulation of TRPM8 expression in DRG in the rat model of AC exposed MIA induced arthritis.