• Toxicological Research
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• 제35권4호
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• pp.403-410
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• 2019

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

• Molecules and Cells
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• 제45권4호
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• pp.169-176
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• 2022

A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular signaling. An interesting linkage between cilia and obesity has been revealed by studies of the human genetic ciliopathies Bardet-Biedl syndrome and Alström syndrome, in which obesity is a principal manifestation. Mouse models of cell type-specific cilia dysgenesis have subsequently demonstrated that ciliary defects restricted to specific hypothalamic neurons are sufficient to induce obesity and hyperphagia. A potential mechanism underlying hypothalamic neuron cilia-related obesity is impaired ciliary localization of G protein-coupled receptors involved in the regulation of appetite and energy metabolism. A well-studied example of this is melanocortin 4 receptor (MC4R), mutations in which are the most common cause of human monogenic obesity. In the paraventricular hypothalamus neurons, a blockade of ciliary trafficking of MC4R as well as its downstream ciliary signaling leads to hyperphagia and weight gain. Another potential mechanism is reduced leptin signaling in hypothalamic neurons with defective cilia. Leptin receptors traffic to the periciliary area upon leptin stimulation. Moreover, defects in cilia formation hamper leptin signaling and actions in both developing and differentiated hypothalamic neurons. The list of obesity-linked ciliary proteins is expending and this supports a tight association between cilia and obesity. This article provides a brief review on the mechanism of how ciliary defects in hypothalamic neurons facilitate obesity.

• 대한본초학회지
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• 제38권1호
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• pp.45-53
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• 2023

Objectives : Network pharmacology-based research is one of useful tool to predict the possible efficacy and molecular mechanisms of natural materials with multi compounds-multi targeting effects. In this study, we investigated the functional underlying mechanisms of Astragalus membranaceus Bunge (AM) on its anti-obesity effects using a network pharmacology analysis. Methods : The constituents of AM were collected from public databases and its target genes were gathered from PubChem database. The target genes of AM were compared with the gene set of obesity to find the correlation. Then, the network was constructed by Cytoscape 3.9.1. and functional enrichment analysis was conducted to predict the most relevant pathway of AM. Results : The result showed that AM network contained the 707 nodes and 6867 edges, and 525 intersecting genes were exhibited between AM and obesity gene set, indicating that high correlation with the effects of AM on obesity. Based on GO biological process and KEGG Pathway, 'Response to lipid', 'Cellular response to lipid', 'Lipid metabolic process', 'Regulation of chemokine production', 'Regulation of lipase activity', 'Chemokine signaling pathway', 'Regulation of lipolysis in adipocytes' and 'PPAR signaling pathway' were predicted as functional pathways of AM on obesity. Conclusions : AM showed high relevance with the lipid metabolism related with the chemokine production and lipolysis pathways. This study could be a basis that AM has promising effects on obesity via network pharmacology analysis.

• Clinical Nutrition Research
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• 제12권2호
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• pp.154-167
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• 2023

Hepatic encephalopathy (HE) associated with liver failure is accompanied by hyperammonemia, severe inflammation, depression, anxiety, and memory deficits as well as liver injury. Recent studies have focused on the liver-brain-inflammation axis to identify a therapeutic solution for patients with HE. Lipocalin-2 is an inflammation-related glycoprotein that is secreted by various organs and is involved in cellular mechanisms including iron homeostasis, glucose metabolism, cell death, neurite outgrowth, and neurogenesis. In this study, we investigated that the roles of lipocalin-2 both in the brain cortex of mice with HE and in Neuro-2a (N2A) cells. We detected elevated levels of lipocalin-2 both in the plasma and liver in a bile duct ligation mouse model of HE. We confirmed changes in cytokine expression, such as interleukin-1β, cyclooxygenase 2 expression, and iron metabolism related to gene expression through AKT-mediated signaling both in the brain cortex of mice with HE and N2A cells. Our data showed negative effects of hepatic lipocalin-2 on cell survival, iron homeostasis, and neurite outgrowth in N2A cells. Thus, we suggest that regulation of lipocalin-2 in the brain in HE may be a critical therapeutic approach to alleviate neuropathological problems focused on the liver-brain axis.

• International Journal of Oral Biology
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• 제49권3호
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• pp.53-60
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• 2024

Nicotinamide (NAM), a water-soluble derivative of vitamin B3, has emerged as a potential therapeutic agent for bone-related disorders. In particular, it promotes bone metabolism and alleviates delayed tooth eruptions associated with cleidocranial dysplasia (CCD). NAM serves as a precursor for nicotinamide adenine dinucleotide, a key coenzyme involved in cellular metabolism that plays an essential role in oxidative phosphorylation and mitochondrial function. Recent research has highlighted the capacity of NAM to enhance osteogenic differentiation and regulate the interaction between osteoblasts and osteoclasts, which is critical for maintaining bone homeostasis. Moreover, the effect of NAM in preventing delayed tooth eruptions in CCD models underscores its potential as a noninvasive therapeutic option. Considering its safety profile and therapeutic potential, NAM is a promising candidate for long-term treatment of bone diseases and prevention of age-related bone disorders.

• Journal of Radiation Protection and Research
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• 제43권2호
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• pp.66-74
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• 2018

Background: Tumor response to anticancer therapies can much be influenced by microenvironmental factors. In this study, we determined the effect of these microenvironmental factors on DNA methylation using A549 human lung adenocarcinoma cell line. Materials and Methods: We subjected A549 cells to various conditions mimicking tumor microenvironment including hypoxia, acidosis (sodium lactate), oxidative stress ($H_2O_2$), bystander effect (supernatant from doxorubicin (Dox)-treated or irradiated cells), and immune cell infiltration (supernatant from THP-1 or Jurkat T cells). Genomic DNA was isolated from these cells and analyzed for DNA methylation. Clonogenic cell survival, gene expression, and metabolism were analyzed in cells treated with some of these conditions. Results and Discussion: We found that DNA methylation level was significantly decreased in A549 cells treated with conditioned media from Dox-treated cells or Jurkat T cells, or sodium lactate, indicating an active transcription. To determine whether the decreased DNA methylation affects radiation sensitivity, we exposed cells to these conditions followed by 6 Gy irradiation and found that cell survival was significantly increased by sodium lactate while it was decreased by conditioned media from Dox-treated cells. We further observed that cells treated with conditioned media from Dox-treated cells exhibited significant changes in expression of genes including BAX and FAS (involved in apoptosis), NADPH dehydrogenase (mitochondria), EGFR (cellular survival) and RAD51 (DNA damage repair) while sodium lactate increased cellular metabolism rather than changing the gene expression. Conclusion: Our results suggest that various tumor microenvironmental factors can differentially influence DNA methylation and hence radiosensitivity and gene expression in A549 cancer cells.

• Asian-Australasian Journal of Animal Sciences
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• 제13권1호
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• pp.115-125
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• 2000

In recent years a great deal of information has accumulated for livestock on vitamin. function, metabolism and supplemental needs. The role of the antioxidant "vitamins" (carotenoids, vitamin E and vitamin C) in immunity and health of livestock has been a fruitful area of research. These nutrients play important roles in animal health by inactivating harmful free radicals produced through normal cellular activity and from various stressors. Both in vitro and in vivo studies showed that these antioxidant vitamins generally enhance different aspects of cellular and noncellular immunity. A compromised immune system will result in reduced animal production efficiency through increased susceptibility to diseases, thereby leading to increased animal morbidity and mortality. Vitamin E has been shown to increase performance of feedlot cattle and to increase immune response for ruminant health, including being beneficial for mastitis control. Vitamin E given to finishing cattle at higher than National Research Council (NRC) requirements dramatically maintained the red color (oxymyoglobin) compared with the oxidized metmyoglobin of beef. Under commercial livestock and poultry production conditions, vitamin allowances higher than NRC requirements may be needed to allow optimum performance. Generally, the optimum vitamin supplementation level is the quantity that achieves the best growth rate, feed utilization, health (including immune competency), and provides adequate body reserves.

• Journal of Microbiology and Biotechnology
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• 제4권2호
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• pp.146-150
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• 1994

Production of poly-$\beta$-hydroxybutyrate (PHB) in fed-batch fermentation was studied. Utilization of carbon for PHB biosynthesis was investigated by using feeding solutions with different ratios of carbon to nitrogen (C/N). It was observed that at a high C/N ratio carbon source was more preferably utilized for PHB accumulation while its consumption for cellular metabolism appeared to be more favored at a low C/N value. A high cell concentration (184 g/l) was achieved when ammonium hydroxide solution was fed to control the pH, which was also utilized as the sole nitrogen source. For the mass production of PHB, two-stage fed-batch operations were carried out where PHB accumulation was observed to be stimulated by switching the ammonium feeding mode to the nitrogen limiting condition. A large amount of PHB (108 g/l) was obtained with cellular content of 80% within 50 hrs of operation.

• 약학회지
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• 제46권6호
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• pp.466-471
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• 2002

Oxidative stress is considered to be associated with many diseases, such as inflammatory and cardiovascular diseases, aging and cancer. An important etiological mechanism of these diseases may be a causal relationship between the presence of oxidants and the generation of lipid hydroperoxides derived from enzymatic reactions or xenobiotic metabolism. The hydroperoxides can be decomposed to alkoxy- (ROㆍ) and peroxy- (ROOㆍ) free radicals that can oxidize other cell components, resulting in changes in enzyme activity or the generation of mediators, which can cause further cell damage. The aim of this study was to evaluate the ability of aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), to affect cellular response in primary cultures of rat hepatocytes to t-butyl hydroperoxide (t-BHP) induced oxidative stress and hepatotoxicity. CK-treated cells showed an increased resistance to oxidative challenge, as revealed by a higher percent of survival capacity in respect to control cells. CK reduced t-BHP-enhanced lipid peroxidation measured as production of malondialdehyde and enhanced intracellular reduced glutathione depletion by t-BHP. Furthermore, CK protected from the t-BHP-induced intracellular generation of reactive oxygen species assessed by monitoring dichlorodihydrofluorescein fluorescence. It can be concluded that CK exerts an antioxidant action inside the cell, responsible for the observed modulation of the cellular response to oxidative challenge, and CK have a marked antioxidative and hepatoprotective potency.

• 환경생물
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• 제23권2호
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• pp.152-156
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• 2005

Ionizing radiation is a well- known therapy factor for human carcinoma cells. Genotoxic stress mediates cell cycle control, transcription and cellular signaling. In this work, we have used a microarray hybridization approach to characterize the cell type-specific transcriptional response of human carcinoma MCF-7 and HeLa cell line to $\gamma-radiation$, such as 4Gy 4hr. We found that exposure to $\gamma-ray$ alters by at least a $log_2$ factor of 1.0 the expression of known genes. Of the 27 genes affected by irradiation, 11 are down- regulated in MCF-7 cells and 2 genes induced by radiation,15 are repressed in HeLa cells. Many genes were involved in known damage- response pathways for cell cycling, transcription factor and cellular signaling response. However, in MCF-7 cells, we observed gene expression pattern in chromatin, apoptosis, stress, differentiation, cytokine, metabolism, ribosome and calcium. In HeLa cells, it showed clearly the expression changes in adhesion and migration, lysosome, brain, genome instability and translation. These insights reveal new therapy directions for studying the human carcinoma cell response to radiation.