• Journal of Periodontal and Implant Science
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• v.43 no.4
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• pp.191-197
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• 2013

Purpose: Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. Methods: LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory ${\kappa}B$ $(I{\kappa}B)-{\alpha}$ degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. Results: Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. Conclusions: Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-${\kappa}B$ and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.

• The Journal of Korean Medicine
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• v.29 no.2
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• pp.71-80
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• 2008

Objective: There is increasing evidence that chronic non-bacterial prostatitis is recognized to be a local inflammatory disease, and there is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and clinical value in the evaluation of therapeutic efficacy. Prunella vulgaris has been traditionally used in treatment of inflammatory diseases, including of scrofula, goiter, and allergy diseases. In this study, we investigated the effects of Prunella vulgaris on inflammatory cytokines and cytopathological alternation in the rat model of non-bacterial prostatitis induced by castration and $17{\beta}-estradiol$ treatment. Methods: Two-month-old rats were treated with $17{\beta}-estradiol$ after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Prunella vulgaris as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathological parameters including the epithelial score and epithelial-stromal ratio for glandular damage, and the expression of inflammatory cytokine genes including the interleukin $(IL)-1{\beta}$, IL-5, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$. Results: While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Prunella vulgaris showed a diminished range of tissue damage. Epithelial score was improved in Prunella vulgaris over that of the control (P<0.05). The epithelial-stromal ratio was lower with Prunella vulgaris when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytokine genes, Prunella vulgaris inhibited the expression of $IL-1{\beta}$ and $TNF-{\alpha}$ genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions: These findings suggest that Prunella vulgaris may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and promotion of anti-inflammatory cytokine. From theses results, we suggest that Prunella vulgaris could be a useful remedy agent for treating chronic non-bacterial prostatitis.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.391-397
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• 2010

E2F transcription factors and their target genes have been known to play an important role in cell growth control. We found that curcumin, a polyphenolic phytochemical isolated from the plant Curcuma longa, markedly suppressed E2F4 expression in HCT116 colon cancer cells. Hydrogen peroxide was also found to decrease E2F4 protein level, indicating the involvement of reactive oxygen species (ROS) in curucmin-induced downregulation of E2F4 expression. Involvement of ROS in E2F4 downregulation in response to curcumin was confirmed by the result that pretreatment of cells with N-acetylcystein (NAC) before exposure of curcumin almost completely blocked the reduction of E2F4 expression at the protein as well as mRNA level. Anti-proliferative effect of curcumin was also suppressed by NAC which is consistent to previous reports showing curcumin-superoxide production and induction of poly (ADP-ribose) polymerase (PARP) cleavage as well as apoptosis. Expression of several genes, cyclin A, p21, and p27, which has been shown to be regulated in E2F4-dependent manner and involved in the cell cycle progression was also affected by curcumin. Moreover, decreased (cyclin A) and increased (p21 and p27) expression of these E2F4 downstream genes by curcumin was restored by pretreatment of cells with NAC and E2F4 overexpression which is induced by doxycycline. In addition, E2F4 overexpression was observed to partially ameliorate curcumin-induced growth inhibition by cell viability assay. Taken together, we found curcumin-induced ROS down-regulation of E2F4 expression and modulation of E2F4 target genes which finally lead to the apoptotic cell death in HCT116 colon cancer cells, suggesting that E2F4 appears to be a novel determinant of curcumin-induced cytotoxicity.

• Preventive Nutrition and Food Science
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• v.7 no.4
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• pp.454-460
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• 2002

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietary-related alterations of the disease need to be defined to guide public health recommendations to reduce athero-sclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR $\alpha$, $\beta$/$\delta$ and ${\gamma}$, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1347-1355
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• 2004

In this study, the immunological effect of a traditional Korea herbal acupuncture, that has been widely used for the treatment of various immunological disorders including inflammation in Korea, was examined in vitro and in vivo. In our previous study demonstrated that BV increased the expression of IFN-γ mRNA, that plays pivotal role in T cell response. This study was designated to evaluate the effect of BV on helper T cell development by monitoring Th1/Th2 specific cytokine secretion patterns in artificially induced Th1/Th2 polarized condition and in vivo. The results demonstrated that BV didn't have mitogenic effects on the unstimulated CD4+ T cell, but increased the CD4+ T cell proliferation upon activation with anti-CD3/CD28 antibody. The Th1 cells were over-populated dramatically in Th1 driven condition with BV treatment, while the Th2 cells were increased slightly in Th2 skewed condition. Furthermore, under Th1-skewed conditions, the level of IFN-γ was considerably increased with BV treatment. Besides, the expression of T-bet, a transcription factor that plays pivotal role in Th1 lineage programming, was increased with BV treatment. The expressions of IFN-γ and T-bet were also significantly increased in vivo. The results that Th1 specific cytokine secretion were considerably increased and Th2 specific cytokine secretion were not significantly changed in vitro and in vivo indicated that BV enhances Th1 lineage development, Therefore, these results suggest that BV might be desirable agent for correction of Th1 dominant pathological disorders.

• Parasites, Hosts and Diseases
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• v.46 no.3
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• pp.127-132
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• 2008

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.

• BMB Reports
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• v.44 no.8
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• pp.547-552
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• 2011

MED19 is a member of the Mediator that plays a key role in the activation and repression of signal transduction or the regulation of transcription in carcinomas. To tested the functional role of MED19 in human prostate cancer, we downregulated MED19 expression in prostate cancer cells (PC-3 and DU145) by lentivirus-mediated short hairpin (shRNA), and analyzed the effect of inhibition of MED19 on prostate cancer cell proliferation and tumorigenesis. The in vitro prostate cancer cell proliferation, colony formation, and in vivo tumor growth in nude mice xenografts was significantly reduced after the downregulation of MED19. Knockdown of MED19 caused S-phase arrest and induced apoptosis via modulation of Bid and Caspase 7. It was suggested that MED19 serves as a novel proliferation regulator that promotes growth of prostate cancer cells.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.85-100
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• 2011

In order to investigate the efficacy of HYGBH on atopic dermatitis, various immune related factors were studied. The results and conclusions are as follows. Atopic dermatitis symptoms were improved in HYGBH treated group and significant decrease in dermatitis index were observed in 12 and 14 weeks. HYGBH treated group showed significant decrease in CD4+, CD3+/CD69+ immune cell ratio in PBMC by 18% and 40.6% respectively. HYGBH treated group showed significant decrease in CD3+, CD11b+/Gr-1+ immune cell ratio in dorsal skin by 44.6% and 53.1% respectively. HYGBH treated group showed significant decrease in IL-4, IFN-${\gamma}$ in spleen by 29.5%, 7.7% respectively. HYGBH treated group showed decrease in the expression of IL-5, IL-13, IL-17 and histamine by 21%, 9.6%, 14%, and 32.2% respectively. Also the group showed decrease in the expression of IgE by 6.8% respectively. HYGBH treated group showed significant decrease in the transcription of IL-5 and IL-3 mRNA in skin by 35.5% and 23.2% respectively. The results above indicated that treatment of HYGBH improved atopic dermatitis symptoms by anti-oxidant activity as well as immune modulation activity as a clinical evidence. Also, to increase the application of fermented oriental medicine, different fermentation conditions using various microbial strains should be accumulated as the clinical evidence in the future.

• Nutrition Research and Practice
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• v.9 no.4
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• pp.343-349
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• 2015

BACKGROUND/OBJECTIVES: Fermentation of dietary fiber results in production of various short chain fatty acids in the colon. In particular, butyrate is reported to regulate the physical and functional integrity of the normal colonic mucosa by altering mucin gene expression or the number of goblet cells. The objective of this study was to investigate whether butyrate modulates mucin secretion in LS174T human colorectal cells, thereby influencing the adhesion of probiotics such as Lactobacillus and Bifidobacterium strains and subsequently inhibiting pathogenic bacteria such as E. coli. In addition, possible signaling pathways involved in mucin gene regulation induced by butyrate treatment were also investigated. MATERIALS/METHODS: Mucin protein content assay and periodic acid-Schiff (PAS) staining were performed in LS174T cells treated with butyrate at various concentrations. Effects of butyrate on the ability of probiotics to adhere to LS174T cells and their competition with E. coli strains were examined. Real time polymerase chain reaction for mucin gene expression and Taqman array 96-well fast plate-based pathway analysis were performed on butyrate-treated LS174T cells. RESULTS: Treatment with butyrate resulted in a dose-dependent increase in mucin protein contents in LS174T cells with peak effects at 6 or 9 mM, which was further confirmed by PAS staining. Increase in mucin protein contents resulted in elevated adherence of probiotics, which subsequently reduced the adherent ability of E. coli. Treatment with butyrate also increased transcriptional levels of MUC3, MUC4, and MUC12, which was accompanied by higher gene expressions of signaling kinases and transcription factors involved in mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS: Based on our results, butyrate is an effective regulator of modulation of mucin protein production at the transcriptional and translational levels, resulting in changes in the adherence of gut microflora. Butyrate potentially stimulates the MAPK signaling pathway in intestinal cells, which is positively correlated with gut defense.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.572-580
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• 2016

3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.