• IMMUNE NETWORK
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• v.5 no.3
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• pp.150-156
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• 2005

Background: Dendritic cells (DCs) playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of antigen presenting cell (APC) function of DCs, we searched for and characterized APC function modulators from natural products. Methods: DCs were cultured in the presence of propolis components, WP and CP, and then examined for their ability to present exogenous antigen in association with major histocompatibility complexes (MHC). Results: WP and CP inhibited class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells, and DCs generated from bone marrow cells with GM-CSF and IL-4. The inhibitory activity of WP and CP appeared to be due not only to inhibition of phagocytic activity of DCs, but also to suppression of expression of MHC molecules on DCs. We also examined the effects of WP and CP on T cells. Interestingly, WP and CP increased IL-2 production from T cells. Conclusion: These results demonstrate that WP and CP inhibit MHC-restricted presentation of exogenous antigen through down-regulation of phagocytic activity and suppression of expression of MHC molecules on DCs.

• Journal of Periodontal and Implant Science
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• v.50 no.5
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• pp.291-302
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• 2020

Purpose: The objective of this study was to investigate whether phelligridin D could reduce glucose-induced oxidative stress, attenuate the resulting inflammatory response, and restore the function of human periodontal ligament cells (HPDLCs). Methods: Primary HPDLCs were isolated from healthy human teeth and cultured. To investigate the effect of phelligridin D on glucose-induced oxidative stress, HPDLCs were treated with phelligridin D, various concentrations of glucose, and glucose oxidase. Glucose-induced oxidative stress, inflammatory molecules, osteoblast differentiation, and mineralization of the HPDLCs were measured by hydrogen peroxide (H₂O₂) generation, cellular viability, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot analyses. Results: Glucose-induced oxidative stress led to increased production of H₂O₂, with negative impacts on cellular viability, ALP activity, and calcium deposition in HPDLCs. Furthermore, HPDLCs under glucose-induced oxidative stress showed induction of inflammatory molecules (intercellular adhesion molecule-1, vascular cell adhesion protein-1, tumor necrosis factor-alpha, interleukin-1-beta) and disturbances of osteogenic differentiation (bone morphogenetic protein-2, and -7, runt-related transcription factor-2), cementogenesis (cementum protein-1), and autophagy-related molecules (autophagy related 5, light chain 3 I/II, beclin-1). Phelligridin D restored all these molecules and maintained the function of HPDLCs even under glucose-induced oxidative stress. Conclusions: This study suggests that phelligridin D reduces the inflammation that results from glucose-induced oxidative stress and restores the function of HPDLCs (e.g., osteoblast differentiation) by upregulating autophagy.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.15-22
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• 2014

Aggregatibacter actinomycetemcomitans is an important pathogen in the development of localized aggressive periodontitis. Lipopolysaccharide (LPS) is a virulent factor of periodontal pathogens that contributes to alveolar bone loss and connective tissue degradation in periodontal disease. Our present study was designed to investigate the cytokine expression and signaling pathways regulated by A. actinomycetemcomitans LPS (Aa LPS). Cytokine gene expression profiling in RAW 264.7 cells was performed by microarray analyses. The cytokine mRNA and protein levels and related signaling pathways induced by Aa LPS were measured by RT-PCR, ELISA and western blotting. Microarray results showed that Aa LPS strongly induced the expression of NF-${\kappa}B$, NF-${\kappa}B$-related genes, inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in RAW 264.7 cells. NF-${\kappa}B$ inhibitor pretreatment significantly reduced the levels of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA and protein. In addition, the Aa LPS-induced TNF-${\alpha}$ and IL-$1{\beta}$ expression was inhibited by p38/JNK MAP kinase inhibitor pretreatment. These results show that Aa LPS stimulates TNF-${\alpha}$ and IL-$1{\beta}$ expression through NF-${\kappa}B$ and p38/JNK activation in RAW 264.7 cells, suggesting the essential role of this pathway in the pathogenesis of localized aggressive periodontitis.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.123-131
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• 2016

Osteoporosis is a bone pathology leading to increased fracture risk and challenging the quality of life. The aim of this study was to evaluate the effect of an anthraquinone glycoside, aloin, on osteogenic induction of MC3T3-E1 cells. Aloin increased alkaline phosphatase (ALP) activity, an early differentiation marker of osteoblasts. Aloin also increased the ALP activity in adult human adipose-derived stem cells (hADSC), indicating that the action of aloin was not cell-type specific. Alizarin red S staining revealed a significant amount of calcium deposition in cells treated with aloin. Aloin enhanced the expression of osteoblast differentiation genes, Bmp-2, Runx2 and collagen 1a, in a dose-dependent manner. Western blot analysis revealed that noggin and inhibitors of p38 MAPK and SAPK/JNK signals attenuated aloin-promoted expressions of Bmp-2 and Runx2 proteins. siRNA mediated blocking of Wnt-5a signaling pathway also annulled the influence of aloin, indicating Wnt-5a dependent activity. Inhibition of the different signal pathways abrogated the influence of aloin on ALP activity, confirming that aloin induced MC3T3-E1 cells into osteoblasts through MAPK mediated Wnt and Bmp signaling pathway.

• Parasites, Hosts and Diseases
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• v.52 no.6
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• pp.605-612
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• 2014

Toxoplasma gondii is an intracellular protozoan parasite that causes a Th1 cellular immunity. Our previous study showed that T. gondii lysate antigen (TLA) treatment in S180 tumor-bearing mice resulted in tumor reduction by suppressing CD31 expression, a marker of angiogenesis. In the present study, to investigate tumor suppressive effect of TLA under the absence of T lymphocytes, athymic nude mice were compared with euthymic mice in the anti-tumorigenic effect triggered by TLA in CT26 tumors. According to the results, intratumorally injected TLA reduced tumor growth and TIMP-1 level, a metastatic marker, in both euthymic and athymic mice. TLA treatment led to a sharp increase in IL-12 expression in serum cytokine profiling of athymic mice, and increased MyD88 signals in macrophages derived from the bone marrow, implying the activation of innate immunity. The selective induction of IL-12 by TLA treatment had an anti-tumorigenic effect.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.356-361
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• 2017

Houttuyniae Herba is widely used as a cosmetic for enhancing hair growth, and study on promoting mouse hair growth has also been reported. However, studies on the effects of the Houttuyniae Herba on dermal papilla (DP) cells, which play an important role in hair growth, are not well known. For this reason, we studied the effect of Houttuyniae Herba on DP cells. The strong antioxidant activity of Houttuyniae Herba was confirmed by ABTS assay. In the MTS assay, cell viability was reduced to 94.5% in DP cells by treatment of 2 mg/ml concentration of Houttuyniae Herb and cytotoxicity was not observed at 1 mg/ml concentration. The mRNA expression levels of Bone morphogenetic pretein (BMP6), fibroblast growth factor 7 (FGF7), FGF10, and ${\beta}$-galactosidase genes, which are involved in hair growth cycle and hair loss induction, were measured by quantitative RT-PCR after Houttuyniae Herbtreatment. Houttuyniae Herb did not significantly affect mRNA expression of BMP6, FGF7, FGF10, and ${\beta}$-catenin, which are important factors for regulating the hair cycle, including type 1 $5{\alpha}$-reductase. However, mRNA expression of type 2 $5{\alpha}$-reductase, the major cause of male hair loss, was significantly reduced to 56.1% by treatment of Houttuyniae Herbtreatment. Taken together, these results suggest that the Houttuyniae Herbtreatment can help to treat lair loss through removing free radicals and suppression of the expression level of type 2 $5{\alpha}$-reductase in DP cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.9-21
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• 2015

Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer-related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

• Natural Product Sciences
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• v.14 no.1
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• pp.21-26
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• 2008

The leaves of Acanthopanax species have traditionally been used as a tonic and a sedative as well as in the treatment of rheumatism and diabetes. Chiisanoside is the major active lupane triterpenoid of Acanthopanax leaves. To investigate the bioactivities of chiisanoside, which act on bone metabolism, the effects of chiisanoside on the function of osteoblastic MC3T3-E1 cells were studied. Chiisanoside $(0.02{\sim}20\;{\mu}M)$ significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and nodules mineralization in the cells (P < 0.05). The effect of chiisanoside (2 ${\mu}M$) in increasing ALP activity was completely prevented by the presence of tamoxifen, suggesting that the effect of chiisanoside might be partly estrogen receptor mediated. Moreover, cotreatment of p38 inhibitor SB203580 or JNK inhibitor SP600125 inhibited chiisanoside-mediated ALP upregulation, suggesting that the induction of differentiation by chiisanoside is associated with increased activation of p38 and JNK mitogen-activated protein kinases. Our data indicate that the enhancement of osteoblast function by chiisanoside may result in the prevention for osteoporosis.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.434-441
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• 2015

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

• Journal of Pharmacopuncture
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• v.4 no.1
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• pp.65-84
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• 2001

We recently demonstrated that bee venom (BV) injection into acupoint (i.e. Zusanli) produced more potent anti-inflammatory and antinociciptive effect in Freunds adjuvant induced rheumatoid arthritis (RA) model as compared with that of non-acupoint injection(i.e back). However, the precise components underlying BV-induced antinociceptive and/or anti-inflammatory effects have not been fully understood. Therefore, we further investigated the anti-arthritic effect of BV after extracting the whole BV according to solubility (water soluble: BVA, ethylacetate soluble: BVE). Subcutaneous BVA treatment (0.9 mg/kg/day) into Zusanli acupoint was found to dramatically inhibit paw edema and radiological change (i.e. new bone proliferation and soft tissue swelling) caused by Freunds adjuvant injection. In addition, the increase of serum interleukin-6 by RA induction was normalized by the BVA treatment as similar with that of non-arthritic animals. On the other hand, BVA therapy significantly reduced arthritis induced nociceptive behaviors (i.e., nociceptive score for mechanical hyperalgesia and thermal hyperalgesia). Furthermore, BVA treatment significantly suppressed adjuvant induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. However, BVE treatment (0.05 mg/kg/day) has not any anti-inflammatory and anti-nociceptive effect on RA. Based on the present results, we demonstrated that BVA might be a effective fraction in whole BV for long-term treatment of RA-induced pain and inflammation. However, it is clear necessary that further fraction study about BVA was required for elucidating an effective component of BVA.