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1.
ACS Omega ; 8(21): 18543-18553, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37273629

ABSTRACT

One of the most common diseases in women is breast cancer, which has the highest death globally. Surgery, chemotherapy, hormone treatments, and radiation are the current treatment options for breast cancer. However, these options have several adverse side effects. Recently, peptide-based drugs have gained attention as anticancer therapy. Studies report that peptides from biological toxins such as venom and virulent pathogenic molecules have potential therapeutic effects against multiple diseases, including cancers. This study reports on the in vitro anticancer effect of a short peptide, PS9, derived from a virulent protein, glycosyl hydrolase, of an aquatic fungus, Aphanomyces invadans. This peptide arrests MCF-7 proliferation by regulating intercellular reactive oxygen species (ROS) and apoptotic pathways. Based on the potential for the anticancer effect of PS9, from the in silico analysis, in vitro analyses using MCF-7 cells were executed. PS9 showed a dose-dependent activity; its IC50 value was 25.27-43.28 µM at 24 h. The acridine orange/ethidium bromide (AO/EtBr) staining, to establish the status of apoptosis in MCF-7 cells, showed morphologies for early and late apoptosis and necrotic cell death. The 2,7-dichlorodihydrofluorescein diacetate (DCFDA) staining and biochemical analyses showed a significant increase in reactive oxygen species (ROS). Besides, PS9 has been shown to regulate the caspase-mediated apoptotic pathway. PS9 is nontoxic, in vitro, and in vivo zebrafish larvae. Together, PS9 may have an anticancer effect in vitro.

2.
Int J Mol Sci ; 24(8)2023 Apr 17.
Article in English | MEDLINE | ID: mdl-37108530

ABSTRACT

Probiotics provide a range of health benefits. Several studies have shown that using probiotics in obesity treatment can reduce bodyweight. However, such treatments are still restricted. Leuconostoc citreum, an epiphytic bacterium, is widely used in a variety of biological applications. However, few studies have investigated the role of Leuconostoc spp. in adipocyte differentiation and its molecular mechanisms. Therefore, the objective of this study was to determine the effects of cell-free metabolites of L. citreum (LSC) on adipogenesis, lipogenesis, and lipolysis in 3T3-L1 adipocytes. The results showed that LSC treatment reduced the accumulation of lipid droplets and expression levels of CCAAT/ enhancer-binding protein-α & ß (C/EBP-α & ß), peroxisome proliferator-activated receptor-γ (PPAR-γ), serum regulatory binding protein-1c (SREBP-1c), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), resistin, pp38MAPK, and pErk 44/42. However, compared to control cells, adiponectin, an insulin sensitizer, was elevated in adipocytes treated with LSC. In addition, LSC treatment increased lipolysis by increasing pAMPK-α and suppressing FAS, ACC, and PPAR-γ expression, similarly to the effects of AICAR, an AMPK agonist. In conclusion, L. citreum is a novel probiotic strain that can be used to treat obesity and its associated metabolic disorders.


Subject(s)
Adipogenesis , Lipogenesis , Mice , Animals , AMP-Activated Protein Kinases/metabolism , Peroxisome Proliferator-Activated Receptors/metabolism , Cell Differentiation , Signal Transduction , Obesity , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Leuconostoc/metabolism , 3T3-L1 Cells , PPAR gamma/metabolism
3.
Microorganisms ; 11(2)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36838434

ABSTRACT

Infectious diseases caused by bacteria are at risk of spreading and prolonging due to antimicrobial resistance. It is, therefore, urgently necessary to develop a more effective antibiotic alternative strategy to control pathogen spread. In general, probiotics have been recommended as a substitute for antibiotics that inhibit pathogens. This study was isolated and probiotic characteristics and antibacterial bacterial efficiency against various infection-causing pathogens were determined by different in vitro methods. A 16S rRNA sequence confirmed that the isolated strains belonged to a species of Leuconostoc citreum. L. citreum KCC-57 and KCC-58 produced various extracellular enzymes and fermented different carbohydrates. There was significant tolerance for both strains under the harsh conditions of the gastrointestinal tract (GIT). In addition, L. citreum KCC-57 and L. citreum KCC-58 showed significant auto-aggregations and hydrophobicity properties that varied with incubation time. Moreover, the cell-free secondary supernatant (CFS) of L. citreum KCC-57 and L. citreum KCC-58 inhibited growth of Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. According to a co-culture study, L. citreum KCC-57 and L. citreum KCC-58 were highly competitive for pathogen growth. L. citreum KCC-57 and L. citreum KCC-58 showed significant probiotic potential and strong antibacterial activities against different pathogens, suggesting that these strains could be used instead of antibiotics to control infectious pathogens.

4.
Int J Mol Sci ; 23(12)2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35743193

ABSTRACT

The most prevalent chronic liver disorder in the world is fatty liver disease caused by a high-fat diet. We examined the effects of Lactiplantibacillus plantarum-KCC48 on high-fat diet-induced (HFD) fatty liver disease in mice. We used the transcriptome tool to perform a systematic evaluation of hepatic mRNA transcripts changes in high-fat diet (HFD)-fed animals and high-fat diet with L. plantarum (HFLPD)-fed animals. HFD causes fatty liver diseases in animals, as evidenced by an increase in TG content in liver tissues compared to control animals. Based on transcriptome data, 145 differentially expressed genes (DEGs) were identified in the liver of HFD-fed mice compared to control mice. Moreover, 61 genes were differentially expressed in the liver of mice fed the HFLPD compared to mice fed the HFD. Additionally, 43 common DEGs were identified between HFD and HFLPD. These genes were enriched in metabolic processes, retinol metabolism, the PPAR signaling pathway, fatty acid degradation, arachidonic metabolism, and steroid hormone synthesis. Taking these data into consideration, it can be concluded that L. plantarum-KCC48 treatment significantly regulates the expression of genes involved in hepatosteatosis caused by HFD, which may prevent fatty liver disease.


Subject(s)
Diet, High-Fat , Non-alcoholic Fatty Liver Disease , Animals , Diet, High-Fat/adverse effects , Lipid Metabolism/genetics , Liver/metabolism , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Transcriptome
5.
Mater Sci Eng C Mater Biol Appl ; 135: 112673, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35581065

ABSTRACT

Scaffolds combined with bioactive agents can enhance bone regeneration at therapeutic sites. We explore whether combined supplementation with coumaric acid and recombinant human-cartilage oligomeric matrix protein-angiopoietin 1 (rhCOMP-Ang1) is an ideal approach for bone tissue engineering. We developed coumaric acid-conjugated absorbable collagen scaffold (CA-ACS) and investigated whether implanting CA-ACS in combination with rhCOMP-Ang1 facilitates ACS- or CA-ACS-mediated bone formation using a rat model of critically sized mandible defects. We examined the mechanisms by which coumaric acid and rhCOMP-Ang1 regulate behaviors of human periodontal ligament fibroblasts (hPLFs). The CA-ACS exhibits greater anti-degradation and mechanical strength properties than does ACS alone. Implanting CA-ACS loaded with rhCOMP-Ang1 greatly enhances bone regeneration at the defect via the activation of angiogenic, osteogenic, and anti-osteoclastic responses compared with other rat groups implanted with an ACS alone or CA-ACS. Treatment with both rhCOMP-Ang1 and coumaric acid increases proliferation, mineralization, and migration of cultured hPLFs via activation of the Ang1/Tie2 signaling axis at a greater rate than treatment with either of them alone. Collectively, this study demonstrates that CA-ACS impregnated with rhCOMP-Ang1 enhances bone regeneration at therapeutic sites, and this enhancement is associated with a synergistic interaction between rhCOMP-Ang1-mediated angiogenesis and coumaric acid-related antioxidant responses.


Subject(s)
Angiopoietin-1 , Antioxidants , Angiopoietin-1/metabolism , Angiopoietin-1/pharmacology , Animals , Antioxidants/pharmacology , Cartilage Oligomeric Matrix Protein , Collagen/pharmacology , Coumaric Acids , Mandible , Rats
6.
Antioxidants (Basel) ; 10(8)2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34439457

ABSTRACT

While total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliorating or preventing ROS accumulation and oxidative stress is necessary for TBI-requiring clinical treatments. Here, we explored whether administration of ferulic acid, a dietary antioxidant, protects against TBI-mediated systemic damages, and examined the possible mechanisms therein. Sublethal TBI (5 Gy) decreased body growth, lifespan, and production of circulating blood cells in mice, together with ROS accumulation, and senescence induction of BM-conserved HSCs and MSCs. TBI also impaired BM microenvironment and bone mass accrual, which was accompanied by downregulated osteogenesis and by osteoclastogenic and adipogenic activation in BM. Long-term intraperitoneal injection of ferulic acid (50 mg/kg body weight, once per day for 37 consecutive days) protected mice from TBI-mediated mortality, stem cell senescence, and bone mass loss by restoring TBI-stimulated disorders in osteogenic, osteoclastic, and adipogenic activation in BM. In vitro experiments using BM stromal cells supported radioprotective effects of ferulic acid on TBI-mediated defects in proliferation and osteogenic differentiation. Overall, treatment with ferulic acid prevented TBI-mediated liver damage and enhanced endogenous antioxidant defense systems in the liver and BM. Collectively, these results support an efficient protection of TBI-mediated systemic defects by supplemental ferulic acid, indicating its clinical usefulness for TBI-required patients.

7.
Indian J Clin Biochem ; 34(1): 68-75, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30728675

ABSTRACT

The aims of this study were to explore whether a phenolic acid and flavonoid fraction (named PAFF) isolated from Lolium multiflorum Lam. protects against d-galactosamine (GalN)-induced liver damages in mice and to investigate the associated mechanisms. ICR mice received oral administration with various concentrations (50, 100, and 200 mg/kg body weight) of PAFF once per 2 days for seven times before intraperitoneal injection with 800 mg/kg GalN. After a day of GalN challenge, blood and tissue samples were analyzed by biochemical, histopathological, real time RT-PCR, and Western blot methods. GalN challenge induced severe damage to hepatocytes with hepatocellular vacuolization and necrosis. GalN treatment increased serum ALT, ALP, AST, and LDH levels and hepatic MDA levels and stimulated mRNA and protein expressions of Nrf2 and HO-1 in the liver. GalN treatment also diminished the levels of GSH and the activities of CAT, SOD, and GPx in the liver. However, combined treatment with PAFF inhibited GalN-mediated increases in the histological damages and the levels of serum enzymes and hepatic MDA, restored the activities of hepatic antioxidant enzymes up to those in the control values, and augmented the GalN-stimulated expression of Nrf2 and HO-1 in the liver. Furthermore, PAFF treatment alone increased the cellular SOD activity and the expression of Nrf2 and HO-1 in the liver. Our results suggest that PAFF may protect against GalN-induced liver damage by decreasing oxidative stress and increasing cellular antioxidant activities through an activation of Nrf2/HO-1-dependent pathway.

8.
Food Sci Biotechnol ; 26(1): 279-285, 2017.
Article in English | MEDLINE | ID: mdl-30263539

ABSTRACT

Dietary hydroxycinnamates are considered as attractive materials for radioprotection. This study explores whether hydroxycinnamates protect against γ-radiation-induced cellular damages and hematopoietic stem cell senescence. C57BL/6 mice were orally administered with each of caffeic acid, p-coumaric acid, and ferulic acid (20mg/kg body weight) once per three days for five times before exposure to total body radiation (5 Gy). Irradiation increased the activities of alanine amino transaminase and aspartate aminotransferase in blood serum but decreased the anti-oxidant defense enzyme activities in the liver and spleen tissues. Oral administration of the compounds almost completely prevented irradiation-mediated changes in these enzyme activities. The hydroxycinnamates also inhibited the irradiation-mediated increases in the mitochondrial superoxide anions of Lin-Sca-1+c-Kit+ (LSK) cells and CD150+CD48- LSK cells in the bone marrow. These results suggest that dietary hydroxycinnamates protect against irradiation-mediated oxidative damages of tissues and bone marrow progenitor cells.

9.
Pharm Biol ; 55(1): 611-619, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27937124

ABSTRACT

CONTEXT: Interest has recently renewed in using Lolium multiflorum Lam. (Poaceae) (called Italian ryegrass; IRG) silage as an antioxidant and anti-inflammatory diet. OBJECTIVE: This study investigated the antioxidant, anti-inflammatory and anti-septic potential of IRG silage and identified the primary components in IRG active fractions. MATERIALS AND METHODS: Total 16 fractions were separated from the chloroform-soluble extract of IRG aerial part using Sephadex LH-20 column before HPLC analysis. Antioxidant and anti-inflammatory activities of the fractions at doses of 0-100 µg/mL were investigated using various cell-free and cell-mediated assay systems. To explore anti-septic effect of IRG fractions, female ICR and BALB/c mice orally received 40 mg/kg of phenolic acid and flavonoid-rich active fractions F7 and F8 every other day for 10 days, respectively, followed by LPS challenge. RESULTS: The active fractions showed greater antioxidant and anti-inflammatory potential compared with other fractions. IC50 values of F7 and F8 to reduce LPS-stimulated NO and TNF-α production were around 15 and 30 µg/mL, respectively. Comparison of retention times with authentic compounds through HPLC analysis revealed the presence of caffeic acid, ferulic acid, myricetin and kaempferol in the fractions as primary components. These fractions inhibited LPS-stimulated MAPK and NF-κB activation. Supplementation with F7 or F8 improved the survival rates of mice to 70 and 60%, respectively, in LPS-injected mice and reduced near completely serum TNF-α and IL-6 levels. DISCUSSION AND CONCLUSION: This study highlights antioxidant, anti-inflammatory and anti-septic activities of IRG active fractions, eventually suggesting their usefulness in preventing oxidative damage and inflammatory disorders.


Subject(s)
Anti-Infective Agents, Local/pharmacology , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Flavonoids/pharmacology , Hydroxybenzoates/pharmacology , Inflammation/prevention & control , Lolium/chemistry , Macrophages/drug effects , Plant Extracts/pharmacology , Sepsis/prevention & control , Animals , Anti-Infective Agents, Local/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Chromatography, High Pressure Liquid , Disease Models, Animal , Female , Flavonoids/isolation & purification , Hydroxybenzoates/isolation & purification , Inflammation/chemically induced , Inflammation/metabolism , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred ICR , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , RAW 264.7 Cells , Sepsis/chemically induced , Sepsis/metabolism , Silage , Solvents/chemistry , Time Factors , Tumor Necrosis Factor-alpha/metabolism
10.
J Ethnopharmacol ; 179: 55-65, 2016 Feb 17.
Article in English | MEDLINE | ID: mdl-26721217

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Water extract of Raphanus sativus L. (RSL) seeds was traditionally used to treat digestive inflammatory complaints in Korean culture. RSL seeds exerted antioxidant, anti-inflammatory, and anti-septic functions, suggesting their pharmacological potential for the treatment of inflammatory pathologies associated with oxidative stress such as inflammatory bowel disease. AIM OF THIS STUDY: We evaluated the intestinal anti-inflammatory effects of RSL seed water extract (RWE) in experimental rat models of trinitrobenzenesulphonic acid (TNBS)- or dextran sodium sulfate (DSS)-induced colitis. MATERIALS AND METHODS: RWE was characterized by determining the content of sinapic acid as a reference material and then assayed in the DSS and TNBS models of rat colitis. Male Sprague-Dawley rats were divided into 10 groups (n=7/group): non-colitic control, DSS or TNBS control, DSS colitis groups treated with RWE (100mg/kg) or mesalazine (25mg/kg), and TNBS colitis groups treated with various doses (10, 40, 70, and 100mg/kg) of RWE or mesalazine (25mg/kg). RWE or mesalazine treatment started the same day of colitis induction and rats were sacrificed 24h after the last treatment followed by histological and biochemical analyses. RESULTS: Oral administration with RWE suppressed intestinal inflammatory damages in both DSS- and TNBS-induced colitic rats. The treatment with 100mg/kg RWE recovered intestinal damages caused by TNBS or DSS to levels similar to that of mesalazine, decreasing the activity of myeloperoxidase activity and the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. RWE treatment inhibited malondialdehyde production and glutathione reduction in colon of colitis rats. The administration of RWE at dose of 100mg/kg also suppressed the TNBS- or DSS-stimulated expression of TNF-α, IL-1ß, monocyte chemotactic protein-1, inducible nitric oxide, and intercellular adhesion molecule-1. Furthermore, RWE inhibited p38 kinase and DNA-nuclear factor-κB binding activities, both of which were stimulated in the colitic rats. CONCLUSIONS: The current findings show that RWE ameliorates intestinal oxidative and inflammatory damages in DSS and TNBS models of rat colitis, suggesting its beneficial use for the treatment of intestinal inflammatory disorders.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colitis, Ulcerative/drug therapy , Plant Extracts/therapeutic use , Raphanus/chemistry , Animals , Body Weight/drug effects , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Colon/pathology , Cytokines/metabolism , Dextran Sulfate , Dose-Response Relationship, Drug , Inflammation Mediators/metabolism , Male , Mesalamine/therapeutic use , Rats , Rats, Sprague-Dawley , Seeds/chemistry , Trinitrobenzenesulfonic Acid , Water
11.
Anim Sci J ; 87(4): 584-90, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26388291

ABSTRACT

This study aimed to identify the genes associated with the development of the rumen epithelium by screening for candidate genes by digital differential display (DDD) in silico. Using DDD in NCBI's UniGene database, expressed sequence tag (EST)-based gene expression profiles were analyzed in rumen, reticulum, omasum, abomasum and other tissues in cattle. One hundred and ten candidate genes with high expression in the rumen were derived from a library of all tissues. The expression levels of 11 genes in all candidate genes were analyzed in the rumen, reticulum, omasum and abomasum of nine Japanese Black male calves (5-week-old pre-weaning: n = 3; 15-week-old weaned calves: n = 6). Among the 11 genes, only 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), aldo-keto reductase family 1, member C1-like (AKR1C1), and fatty acid binding protein 3 (FABP3) showed significant changes in the levels of gene expression in the rumen between the pre- and post-weaning of calves. These results indicate that DDD analysis in silico can be useful for screening candidate genes related to rumen development, and that the changes in expression levels of three genes in the rumen may have been caused by weaning, aging or both.


Subject(s)
Cattle/growth & development , Cattle/genetics , Gene Expression Profiling/methods , Gene Expression , Genetic Association Studies/veterinary , Genetic Testing/methods , Rumen/growth & development , 20-Hydroxysteroid Dehydrogenases/genetics , Aging/genetics , Animals , Computer Simulation , Epithelium/growth & development , Expressed Sequence Tags , Fatty Acid Binding Protein 3 , Fatty Acid-Binding Proteins/genetics , Hydroxymethylglutaryl-CoA Synthase/genetics , Male , Organ Specificity/genetics , Weaning
12.
Anim Sci J ; 87(2): 202-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26278910

ABSTRACT

Six growing lambs were used to evaluate the feeding value of two forage-based diets in a long-term feeding period by measuring body weight (BW) gain, digestibility, nitrogen (N) retention and microbial N (MBN) yield. The animals were fed imported low-quality timothy hay (TH) with concentrate diet (THD) or imported low-quality Italian ryegrass straw (IR) with concentrate diet (IRD) for 9 months. The forages were offered at 2% BW, and concentrate was fed at 40% of forage intake. The BW gain averaged 82.6 and 66.2 g/day for THD and IRD, respectively, without showing significant difference. Average forage intake (% BW) was significantly greater for IR than for TH, although it was not affected by feeding periods. The digestibility did not differ between diets or periods. The numerically greater (P = 0.06) ratio of retained N to absorbed N for IRD than that for THD was prominent. Neither diet nor period had significant effect on MBN supply and efficiency of MBN synthesis. The results suggest that the IR-based diet can be also used for long-term periods of feeding to growing ruminant animals as a grass hay-based diet without any detrimental effects on nutrient utilization and growth performance.


Subject(s)
Animal Feed , Animal Nutritional Physiological Phenomena/physiology , Lolium , Nitrogen/metabolism , Phleum , Sheep/growth & development , Sheep/physiology , Animals , Digestion/physiology , Male , Weight Gain
13.
Food Sci Biotechnol ; 25(1): 349-353, 2016.
Article in English | MEDLINE | ID: mdl-30263277

ABSTRACT

Red beans comprise part of the diet in Korean culture. Anti-inflammatory and anti-septic activities of the butanol fraction of red bean ethanol extracts (BF-RBEE) are known. The intestinal antiinflammatory activity of BF-RBEE and related mechanisms were studied using a rat model of acetic acid-induced colitis. Oral treatment with BF-RBEE (100 mg/kg of body weight) suppressed body weight loss and intestinal inflammatory damage in colitic rats. BF-RBEE treatment reduced the myeloperoxidase activity and the malondialdehyde level that were increased in colitic rats, and restored the reduced level of glutathione. BF-RBEE also inhibited acetic acid-mediated increases in mRNA levels of nitric oxide synthase, interleukin-1ß, and tumor necrosis factor-α. Similarly, treatment with 1mg/kg of prednisolone protected rats against intestinal colitic damage with corresponding decreases in levels of these inflammatory indicators. Red beans can be useful for treatment of intestinal inflammatory diseases.

14.
Biochem Biophys Res Commun ; 466(3): 283-8, 2015 Oct 23.
Article in English | MEDLINE | ID: mdl-26342800

ABSTRACT

Chemerin is a chemoattractant cytokine (chemokine) produced by adipocytes and hepatocytes; it regulates insulin sensitivity and adipocyte differentiation. The objective of this study was to investigate the effect of chemerin on the expression of genes related to lactogenesis and the regulators of chemerin signaling in a bovine mammary epithelial cell line (MAC-T). Two types of chemerin receptors, chemokine like-receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2), were detected in cultured MAC-T cells, whereas chemerin was not detected. G protein-coupled receptor 1 (GPR1), another receptor of chemerin, was undetectable in MAC-T cells. Chemerin upregulated transcript expression of CMKLR1, CCRL2, and genes associated with fatty acid synthesis, glucose uptake, insulin signaling, and casein synthesis in MAC-T cells. Lactogenic hormones (insulin, growth hormone, and prolactin) downregulated the expression of CMKLR1 in MAC-T cells. Adiponectin suppressed CMKLR1 expression. TNF-α suppressed CMKLR1, but induced CCRL2 expression. These data suggest chemerin is a novel regulator of lactogenesis via its own receptor in bovine mammary epithelial cells.


Subject(s)
Chemokines/metabolism , Gene Expression Regulation , Mammary Glands, Animal/metabolism , Milk/metabolism , Receptors, Chemokine/metabolism , Adipocytes/metabolism , Adiponectin/metabolism , Animals , Cattle , Cell Proliferation , Cells, Cultured , Chemotactic Factors/metabolism , Down-Regulation , Female , Gene Expression Profiling , Hormones/metabolism , Tumor Necrosis Factor-alpha/metabolism
15.
J Nanosci Nanotechnol ; 15(2): 1130-4, 2015 Feb.
Article in English | MEDLINE | ID: mdl-26353622

ABSTRACT

Caffeic acid-conjugated chitosan (ChitoCFA) and carboxymethyl dextran-b-poly(ethylene gycol) (CMD-PEG) copolymer were synthesized to fabricate self-organized nanoparticles. Nanoparticles were formed through ion-complex formation between ChitoCFA and CMD-PEG. Nanoparticles have small sizes ranged about 80 nm~300 nm with spherical shapes. Doxorubicin (DOX) was incorporated into the nanoparticles of ChitoCFA/CMD complexes. Particle sizes were increased according to the contents of drug. At drug release experiment, DOX was continuously released over 96 h. Anticancer acticity of nanoparticles were assessed with DOX-resistant CT26 cells. CT26 cells treated with DOX-incorporated nanoparticles revealed strong fluorescence intensity while free DOX revealed weak fluorescence intensity, indicating that DOX-loaded nanoparticles of ChitoCFA/CMD are promising vehicle for anticancer drug targeting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chitosan/chemistry , Nanocapsules/administration & dosage , Nanocapsules/chemistry , Nanoconjugates/chemistry , Neoplasms, Experimental/drug therapy , Antioxidants/administration & dosage , Caffeic Acids/administration & dosage , Cell Line, Tumor , Cell Survival/drug effects , Diffusion , Doxorubicin/administration & dosage , Humans , Nanocapsules/ultrastructure , Nanoconjugates/ultrastructure , Neoplasms, Experimental/pathology , Particle Size , Polyethylene Glycols , Treatment Outcome
16.
BMB Rep ; 48(11): 636-41, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26303969

ABSTRACT

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC.


Subject(s)
Acetylcysteine/pharmacology , Acetylcysteine/therapeutic use , Hydrogen Peroxide/antagonists & inhibitors , Hydrogen Peroxide/pharmacology , NF-E2-Related Factor 2/metabolism , 3T3 Cells , Animals , Cell Differentiation/drug effects , Core Binding Factor Alpha 1 Subunit/metabolism , Down-Regulation/drug effects , Heme Oxygenase-1/metabolism , Humans , Mice , Osteoblasts , Osteocalcin/metabolism , Osteogenesis/drug effects , Oxidative Stress/drug effects , Signal Transduction/drug effects
17.
Anim Sci J ; 86(11): 943-51, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26153850

ABSTRACT

The objective of the present study was to conduct an adipogenic evaluation of different roughage sources and feeding levels during ruminant adipocyte differentiation in vitro. Six wether sheep were divided into a timothy hay feeding group (TFG, n = 3) and an Italian ryegrass straw feeding group (IFG, n = 3). The sheep were fed high-roughage (HR), medium roughage (MR) and low-roughage (LR) diets in a one-way layout design each over a 6-day period. Sheep serum samples collected on the last day of each dietary treatment were added to an adipogenic induction medium for differentiation of preadipocytes derived from sheep subcutaneous adipose tissue. The cytoplasmic lipid accumulations in the TFG serum-treated preadipocytes were significantly higher than those of the IFG-serum treated preadipocytes on day 12. Messenger RNA expression of CCAAT/enhancer-binding protein (C/EBP)-α, C/EBP-ß, C/EBP-δ, fatty-acid-binding protein (aP2) and stearoyl-coenzyme A desaturase (SCD) were regulated by each serum treatment. This study shows that different roughage source diets and roughage-to-concentrate ratio diets can regulate adipocyte differentiation via ruminant blood composition.


Subject(s)
Adipocytes/cytology , Adipocytes/metabolism , Adipogenesis , Animal Feed , Dietary Fiber , Sheep/metabolism , Adipose Tissue/cytology , Animals , Cell Differentiation , Cells, Cultured , Culture Media , Cytoplasm/metabolism , Lipid Metabolism , Male , Subcutaneous Tissue
18.
J Med Food ; 18(3): 314-23, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25469660

ABSTRACT

Rice (Oryza sativa L.) has been a major dietary staple worldwide for centuries. Growing interest in the beneficial effects of antioxidants has inspired investigation of rice hulls as an attractive source of chemopreventive compounds for breast cancer intervention. We prepared methanol extracts from rice hulls of three Korean bred cultivars (japonica), Ilpum, Heugjinju, and Jeogjinju, and one japonica weedy rice, WD-3. We examined the antiproliferative potential of the hull extracts on MCF-7 human breast cancer cells and the related mechanisms thereof. Hull extracts inhibited proliferation of the cells and mediated G0/G1 phase arrest by suppressing cyclins and cyclin-dependent kinases, where WD-3 extract showed the most potent. Blockage of p21 expression by small interfering RNA transfection attenuated G1 phase arrest induced by WD-3 extract. The WD-3 extract exhibited greater antioxidant potential and total phenolic compounds, compared with other rice hulls. Gas chromatography-mass spectrometry analysis for the F4 fractioned from WD-3 extract revealed that cinnamic acid derivatives were the major active constituents. The F4 fraction most potently inhibited proliferation of MCF-7 cells than WD-3 extract through the suppression of cell cycle regulatory factors. Collectively, our results suggest that the pigmented rice hulls possess greater antioxidant and chemopreventive activity against breast cancer than the other rice cultivars tested, demonstrating that WD-3 rice hulls are an attractive source of chemopreventive bioactive compounds.


Subject(s)
Antioxidants/therapeutic use , Breast Neoplasms/drug therapy , Cell Cycle Checkpoints/drug effects , Oryza/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Seeds/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Antioxidants/analysis , Antioxidants/pharmacology , Cell Proliferation/drug effects , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , Female , G1 Phase/drug effects , Humans , MCF-7 Cells , Oryza/classification , Phenols/analysis , Phenols/pharmacology , Phenols/therapeutic use , Plant Extracts/pharmacology , Species Specificity
19.
J Pharm Sci ; 104(1): 144-54, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25417897

ABSTRACT

The aim of this study is to fabricate caffeic acid phenethyl ester (CAPE)-incorporated nanoparticles using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (CE) copolymer and to study their antitumor activity against pulmonary metastasis model of CT26 colon carcinoma cells. CAPE-incorporated nanoparticles showed spherical shapes having small diameters less than 300 nm and CAPE was continuously released from CE nanoparticles over 4 days. CAPE-incorporated polymeric micelles properly inhibited proliferation and induced apoptosis of CT26 cells as well as CAPE itself. Furthermore, they showed similar anti-invasive and antimigrative effect against CT26 cells at in vitro compared with CAPE itself, indicating that CAPE-incorporated nanoparticles have at least equivalent anticarcinogenic activity against CT26 cells compared with CAPE itself. At pulmonary metastasis model of CT26 cells using nude mouse, CAPE-incorporated nanoparticles have superior antimetastatic efficacy against, that is, control treatment with pulmonary metastasis model showed significant increase of lung weight because of the metastasis of tumor cells, whereas CAPE or CAPE-incorporated nanoparticles properly inhibited metastasis of tumor cells. We suggest CAPE-incorporated nanoparticles as a promising candidate for antimetastatic chemotherapeutic agent. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:144-154, 2015.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Caffeic Acids/administration & dosage , Carcinoma/drug therapy , Drug Carriers/administration & dosage , Lung Neoplasms/drug therapy , Nanoparticles/chemistry , Phenylethyl Alcohol/analogs & derivatives , Animals , Anticarcinogenic Agents/adverse effects , Anticarcinogenic Agents/pharmacology , Anticarcinogenic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Caffeic Acids/adverse effects , Caffeic Acids/pharmacology , Caffeic Acids/therapeutic use , Carcinoma/pathology , Carcinoma/secondary , Cell Line, Transformed , Cell Line, Tumor , Cell Movement/drug effects , Colorectal Neoplasms/pathology , Drug Carriers/adverse effects , Drug Carriers/pharmacology , Drug Carriers/therapeutic use , Drug Compounding , Lung/drug effects , Lung/pathology , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Macrophages/drug effects , Macrophages/immunology , Mice , Mice, Inbred BALB C , Micelles , Nanoparticles/adverse effects , Neoplasm Transplantation , Phenylethyl Alcohol/administration & dosage , Phenylethyl Alcohol/adverse effects , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Solubility , Tumor Burden/drug effects
20.
Int Immunopharmacol ; 23(2): 726-34, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25467201

ABSTRACT

The seeds of Raphanus sativus L. (RSL) have long been used as anti-inflammatory traditional medicine. However, scientific bases for the purported potential of the medicine and the associated mechanisms were barely defined. This study investigated the effects of RSL seeds on lipopolysaccharide (LPS)-stimulated inflammatory responses in vitro and in vivo. Treatment with 100 µg/ml ethyl acetate fraction (REF), which was isolated from water extract of the seeds, significantly inhibited LPS-stimulated production of nitric oxide (P < 0.05), interleukin-6 (P < 0.001), and tumor necrosis factor (TNF)-α (P < 0.001) in RAW264.7 cells. Oral supplementation with 30 mg/kg REF protected mice by 90% against LPS-induced septic death and prevented the increases of serum TNF-α and interferon-γ levels in LPS-injected mice. When REF was divided into four sub-fractions (REF-F1-F4), REF-F3 showed the greatest activity to suppress LPS-stimulated production of inflammatory mediators. We subsequently isolated an active fraction from the REF-F3 and identified sinapic acid as the main constituent. The addition of 50 µg/ml active fraction markedly inhibited LPS-stimulated production of inflammatory mediators by suppressing p38 MAPK and nuclear factor-κB activation. Furthermore, supplementation with the active fraction (10 mg/kg) improved the survival rate of LPS-injected mice by 80% of the untreated control. Additional experiments revealed that sinapic acid was the active component responsible for the anti-inflammatory potential of RSL seeds. Collectively, our current results suggest that both RSL seeds and sinapic acid may be attractive materials for treating inflammatory disorders caused by endotoxins.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , MAP Kinase Signaling System/drug effects , NF-kappa B/metabolism , Plant Extracts/therapeutic use , Raphanus/chemistry , Sepsis/drug therapy , Animals , Anti-Inflammatory Agents/administration & dosage , Antioxidants/metabolism , Cell Line , Cytokines/blood , Female , Lipopolysaccharides/toxicity , Macrophages/drug effects , Macrophages/immunology , Mice, Inbred ICR , Nitric Oxide/metabolism , Plant Extracts/administration & dosage , Seeds/chemistry , Sepsis/chemically induced , Sepsis/enzymology , Sepsis/immunology
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