• Korean Journal of Food Science and Technology
• /
• v.49 no.6
• /
• pp.685-692
• /
• 2017

Mitochondrial biogenesis-a process that leads to an increment in the number and density of mitochondria, improves physical performance and body health by enhancing exercise capacity. In the present study, we investigated the stimulatory effect of Ashitaba and red ginseng complex (ARC) on exercise capacity in L6 skeletal muscle cells and mice. In L6 skeletal muscle cells, ARC increased the mitochondrial contents and ATP production by activating AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-$1{\alpha}$) and up-regulating the mRNA expression of nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM). In the animal experiments, mice treated with ARC showed an increment in exercise capacity as compared with mice treated with Ashitaba extract or red ginseng extract alone. These studies indicate that ARC might serve as a potential natural candidate for enhancing exercise capacity by stimulation of mitochondrial biogenesis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.3
• /
• pp.255-261
• /
• 2014

Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and ${\alpha}$-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases ($PKC{\theta}$ and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of $500{\mu}M$ EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-${\beta}$-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.40 no.4
• /
• pp.413-421
• /
• 2014

Corticotropin-releasing factor (CRF) is involved in the stress response and there is increasing evidence that stress influences skin disease such as hair loss. In cultured human hair follicles, CRF inhibits hair shaft elongation, induces premature regression and promotes the apoptosis of hair matrix keratinocytes. We investigated whether CRF influences the dermal papilla cells (DPC) that play pivotal roles in hair growth and cycling. Human DPCs were treated with CRF, adrenocorticotropic hormone (ACTH) and cortisol, key stress hormones along the hypothalamic-pituitary -adrenal (HPA) axis for 1-24 h. Interestingly, CRF modulated the expression of cytokines related to hair growth (KGF, Wnt5a, $TGF{\beta}-2$, Nexin) and increased cAMP production in cultured DPCs. CRF receptors were down-regulated by negative feedback systems. Pretreatment of CRF receptor antagonists or protein kinase A (PKA) inhibitor prevented the CRF-induced modulation. Since the CRF induces proopiomelanocortin (POMC) expression through the cAMP/PKA pathway, we analyzed POMC mRNA. CRF stimulated POMC expression in cultured human DPCs, yet we were unable to detect ACTH levels by western blot. These results indicate that CRF operates within DPCs through CRF receptors along the classical CRF signaling pathway and CRF receptor antagonists could serve as potential therapeutic and cosmetic agents for stress-induced hair loss.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.33 no.1
• /
• pp.1-6
• /
• 2004

$\beta$-Sitosterol is the major phytosterol in higher plants, including fruits and vegetables. The molecule has been shown to have the potential for prevention and therapy for human cancer. We investigated the effects of $\beta$-sitosterol on the cell proliferation of HCT116 human colon cancer cells in order to understand its anti-proliferative mechanism. $\beta$-Sitosterol treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. The anti-proliferative effect of HCT116 cells by $\beta$-sitosterol was associated with formation of apoptotic bodies and degradation of $\beta$-catenin protein. In addition, $\beta$-sitosterol-treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 without alteration in the levels of cyclins and Cdks. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of $\beta$-sitosterol.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.46 no.2
• /
• pp.267-272
• /
• 2017

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

• BMB Reports
• /
• v.51 no.10
• /
• pp.532-537
• /
• 2018

Prostaglandin $E_2$ ($PGE_2$), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because $PGE_2$ functions by signaling through $PGE_2$ receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinase (MMP)-9 as well as the down-regulation of COX-2 expression and $PGE_2$ production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the EP4 antagonist AH23848 prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• Toxicological Research
• /
• v.22 no.1
• /
• pp.23-30
• /
• 2006

Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

• The Journal of the Korean Society for Microbiology
• /
• v.35 no.3
• /
• pp.203-214
• /
• 2000

Porphyromonas gingivalis has been implicated in periodontal diseases. Accumulating evidence suggests that cardiovascular disease is the most prevalent medical problem in patients with periodontal diseases. In order to check the possibility that P. gingivalis is involved in coronary heart disease, the present study was performed to observe P. gingivalis adherence and invasion of human coronary artery endothelial cells (HCAEC) and production of cytokines and growth factors by HCAEC upon P. gingivalis infection. $^3H$-labeled P. gingivalis 381 was incubated with HCAEC for 90 min. The radioactivity of the washed HCAEC was a measure of the absorbed (adhering and invading) P. gingivalis. The absorption radioactivity of the HCAEC infected by P. gingivalis was determined to be 59.58% of the input bacterial cells. In contrast, the absorption radioactivity of the cells infected by S. gordonii Challis which was employed as a control was negligible (0.59%). DPG3, a P. gingivalis mutant defective of fimbriae, appeared to be impaired to some extent in capability of adherence/invasion as compared to that of the parental strain 381, showing 43.04% of the absorption radioactivity. The absorption radioactivity of the HCAEC infected by P. gingivalis 381 in the presence of excessive fimbriae at the concentrations of $50\;{\mu}g$ and $100\;{\mu}g/ml$ was 57.27 and 45.44%, respectively. Invasion of HCAEC by P. gingivalis 381 was observed by an antibiotic (metronidazole) protection assay and transmission electron microscopy (TEM). In the antibiotic protection assay, invasion by the bacterium was measured to be 0.73, 1.09, and 1.51% of the input bacterial cells after incubation for 30, 60, and 90 min, respectively. Invasion by DPG3 was shown to be 0.16% after 90-min incubation. In comparison of invasion efficiency at 90 min of the incubation, the invasion efficiency of DPG3 was 0.37% while that of its parental strain 381 was 2.54%. The immunoblot analysis revealed fimbriae of P. gingivalis did not interact with the surface of HCAEC. These results suggest that fimbriae are not the major contribution to the adherence of P. gingivalis to HCAEC but may be important in the invasion of HCAEC by the bacterium. The presence of cytochalasin D ($1\;{\mu}g/ml$) and staurosporine ($1\;{\mu}M$) reduced the invasion of HCAEC by P. gingivalis 381 by 78.86 and 53.76%, respectively, indicating that cytoskeletal rearrangement and protein kinase of HCAEC are essential for the invasion. Infection of P. gingivalis induced HCAEC to increase the production of TNF-${\alpha}$. by 60.6%. At 90 min of the incubation, the HCAEC infected with P. gingivalis cells was apparently atypical in the shape, showing loss of the nuclear membrane and subcellular organelles. The overall results suggest that P. gingivalis may cause coronary heart disease by adhering to and invading endothelial cells, and subsequently damaging the cells.

• Asian-Australasian Journal of Animal Sciences
• /
• v.31 no.4
• /
• pp.595-606
• /
• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.10
• /
• pp.1450-1457
• /
• 2015

The anti-inflammatory effect of ethanol extracts from Hizikia fusiformis fermented with and without lactic acid bacteria was compared in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages. The fermentation was done using Weissella sp. SH-1 and Lactobacillus casei in a mixture of glucose and lactate source at $30^{\circ}C$ for 30 days. As a result, we confirmed that the fermentation of H. fusiformis with lactic acid bacteria inhibited LPS-stimulated nitric oxide (NO) production and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-6, tumor necrosis factor ${\alpha}$, and IL-$1{\beta}$ as important inflammatory factors. During a comparison analysis, we found that L. casei fermented groups significantly suppressed NO production by regulating iNOS and COX-2 expression. Also, the effective suppression of pro-inflammatory cytokine and LPS-induced activation of mitogen- activated protein kinase indicated that the fermentation using Weissella sp. SH-1 and L. casei may provide an increment towards the extraction of active components, which are effective anti-inflammatory agents.