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1.
Am J Chin Med ; 45(6): 1309-1325, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28830210

RESUMO

Although Arctii Fructus (AF) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of AF on the metastatic properties of colorectal cancer (CRC). The aim of this study was to investigate whether AF could suppress CRC progression by inhibiting cell growth, epithelial-mesenchymal transition (EMT), migration, and the invasion ability of CRC cells. AF decreased proliferation of CRC cells by inducing cell cycle arrest and apoptosis via extrinsic and intrinsic apoptotic pathways. Regarding metastatic properties, AF inhibited EMT by increasing the expression of the epithelial marker, E-cadherin, and decreasing the expression of the mesenchymal marker, N-cadherin, in CT26 cells. Moreover, AF decreased the migration and invasion of CT26 cells by inhibiting matrix metalloproteinase-2 (MMP-2) and MMP-9 activity. We confirmed that the decreased invasion ability and MMP-9 activity by AF treatment involved AMP-activated protein kinase (AMPK) activation. Collectively, this study demonstrates that AF inhibits the proliferation and metastatic properties of CRC cells.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Arctium/química , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Frutas/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Extratos Vegetais/isolamento & purificação
2.
Am J Chin Med ; 45(5): 1047-1060, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28659027

RESUMO

Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text]). In addition, the release of prostaglandin E2 and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1[Formula: see text] expressions in the tumor necrosis factor-[Formula: see text] stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of I[Formula: see text]B and the translocation of the nuclear factor-[Formula: see text]B (NF-[Formula: see text]B). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-[Formula: see text]B transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.


Assuntos
Anti-Inflamatórios , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Eclipta/química , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Mediadores da Inflamação/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Doença Aguda , Animais , Células Cultivadas , Colite/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Feminino , Células HT29 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
3.
PLoS One ; 12(5): e0176937, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28481901

RESUMO

ß-Lapachone is a natural quinone compound from Lapacho trees, which has various pharmacological effects such as anti-bacterial, anti-fungal, anti-viral, and anti-inflammatory activities. However, the effect of ß-lapachone on metastasis of melanoma cells is unclear. In this study, ß-lapachone reduced cell viability of metastatic melanoma cancer cell lines B16F10 and B16BL6 through induction of apoptosis via the mitogen-activated protein kinase (MAPK) pathway. Additionally, flow cytometry results showed that ß-lapachone increased DNA content in the G0/G1 phase of the cell cycle. Analysis of the mechanisms of these events indicated that ß-lapachone regulated the expression of Bcl-2, Bcl-xL, and Bax, resulting in the activation of caspase-3, -8, -9, and poly-ADP-ribose polymerase (PARP). Moreover, the ß-lapachone-administered group showed significantly decreased lung metastasis in the experimental mouse model. In conclusion, our study demonstrates the inhibitory effect of ß-lapachone on lung metastasis of melanoma cells and provides a new insight into the role of ß-lapachone as a potential antitumor agent.


Assuntos
Neoplasias Pulmonares/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/patologia , Naftoquinonas/farmacologia , Metástase Neoplásica/prevenção & controle , Animais , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C57BL
4.
J Ginseng Res ; 41(2): 134-143, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28413317

RESUMO

BACKGROUND: The prevalence of allergic inflammatory diseases such as atopic dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and complete recovery is difficult. Korean Red Ginseng, which is the heat-processed root of Panax ginseng Meyer, is widely and frequently used as a traditional medicine in East Asia. In this study, we investigated whether Korean Red Ginseng water extract (RGE) regulates the expression of proinflammatory cytokines and chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa B (NF-κB) pathway in allergic inflammation. METHODS: Compound 48/80-induced anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin lesion mice models were used to investigate the antiallergic effects of RGE. Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to clarify the effects of RGE on the expression of proinflammatory cytokines and chemokines. RESULTS: Anaphylactic shock and DNFB-induced AD-like skin lesions were attenuated by RGE administration through reduction of serum immunoglobulin E (IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the production of proinflammatory cytokines including IL-1ß, IL-6, and IL-8, and expression of chemokines such as IL-8, thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE decreased the release of tumor necrosis factor-α (TNF-α), IL-1ß, IL-6, and IL-8 as well as expressions of chemokines including macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC-1 cells. Furthermore, our data demonstrated that these inhibitory effects occurred through blockage of the MAPK and NF-κB pathway. CONCLUSION: RGE may be a useful therapeutic agent for the treatment of allergic inflammatory diseases such as AD-like dermatitis.

5.
Integr Cancer Ther ; 16(4): 585-596, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27923905

RESUMO

BACKGROUND: ß-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of ß-lapachone and the underlying mechanisms using colon cancer cells. METHODS: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription-polymerase chain reaction were performed to examine the effects of ß-lapachone on metastatic phenotypes and molecular mechanisms. The effect of ß-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. RESULTS: We found that the inhibition of proliferation of the colon cancer cell lines by ß-lapachone was due to the induction of apoptosis and cell cycle arrest. ß-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of ß-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, ß-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, ß-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, ß-lapachone significantly inhibited the lung metastasis of CT26 cells. CONCLUSIONS: Our results demonstrated the inhibitory effect of ß-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Naftoquinonas/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
6.
Phytomedicine ; 23(13): 1680-1690, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27823633

RESUMO

BACKGROUND: Quercetin is a major dietary flavonoid found in a various fruits, vegetables, and grains. Although the inhibitory effects of quercetin have previously been observed in several types of cancer cells, the anti-metastatic effect of quercetin on colorectal metastasis has not been determined. PURPOSE: This study investigated whether quercetin exhibits inhibitory effect on colorectal lung metastasis. STUDY DESIGN: The effects of quercetin on cell viability, mitogen-activated protein kinases (MAPKs) activation, migration, invasion, epithelial-mesenchymal transition (EMT) and lung metastasis were investigated. METHODS: We investigated the effect of quercetin on metastatic colon cancer cells using WST assay, Annexin V assay, real-time RT-PCR, western blot analysis and gelatin zymography. The anti-metastatic effect of quercetin in vivo was confirmed in a colorectal lung metastasis model. RESULTS: Quercetin inhibited the cell viability of colon 26 (CT26) and colon 38 (MC38) cells and induced apoptosis through the MAPKs pathway in CT26 cells. Expression of EMT markers, such as E-, N-cadherin, ß-catenin, and snail, were regulated by non-toxic concentrations of quercetin. Moreover, the migration and invasion abilities of CT26 cells were inhibited by quercetin through expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulation. Quercetin markedly decreased lung metastasis of CT26 cells in an experimental in vivo metastasis model. CONCLUSION: In conclusion, this study demonstrates for the first time that quercetin can inhibit the survival and metastatic ability of CT26 cells, and it can subsequently suppress colorectal lung metastasis in the mouse model. These results indicate that quercetin may be a potent therapeutic agent for the treatment of metastatic colorectal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/patologia , Neoplasias Pulmonares/tratamento farmacológico , Quercetina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo
7.
Food Funct ; 7(12): 5025-5033, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27882370

RESUMO

Arctii Fructus is traditionally used in oriental pharmacies as an anti-inflammatory medicine. Although several studies have shown its anti-inflammatory effects, there have been no reports on its use in obesity related studies. In this study, the anti-obesity effect of Arctii Fructus was investigated in high-fat diet (HFD)-induced obese mice, and the effect was confirmed in white and primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and reduced the mass of white adipose tissue in HFD-induced obese mice. Serum levels of triglyceride and LDL-cholesterol were reduced, and HDL-cholesterol was increased in the Arctii Fructus treated group. In 3T3-L1 cells, a water extract (WAF) and 70% EtOH extract (EtAF) of Arctii Fructus significantly inhibited adipogenesis and suppressed the expression of proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha. In particular, EtAF activated the phosphorylation of AMP-activated protein kinase. On the other hand, uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, known as brown adipocytes specific genes, were increased in primary cultured brown adipocytes by WAF and EtAF. This study shows that Arctii Fructus prevents the development of obesity through the inhibition of white adipocyte differentiation and activation of brown adipocyte differentiation which suggests that Arctii Fructus could be an effective therapeutic for treating or preventing obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Arctium/química , Gorduras na Dieta/efeitos adversos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Animais , Fármacos Antiobesidade/química , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Molecules ; 21(9)2016 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-27618887

RESUMO

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, ß-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Furanos/farmacologia , Lignanas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica
9.
Artigo em Inglês | MEDLINE | ID: mdl-27143989

RESUMO

This study was performed in order to investigate the antiobese effects of the ethanolic extract of Veratri Nigri Rhizoma et Radix (VN), a herb with limited usage, due to its toxicology. An HPLC analysis identified jervine as a constituent of VN. By an Oil Red O assay and a Real-Time RT-PCR assay, VN showed higher antiadipogenic effects than jervine. In high-fat diet- (HFD-) induced obese C57BL/6J mice, VN administration suppressed body weight gain. The levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα), adipocyte fatty-acid-binding protein (aP2), adiponectin, resistin, and LIPIN1 were suppressed by VN, while SIRT1 was upregulated. Furthermore, VN activated phosphorylation of the liver kinase B1- (LKB1-) AMP-activated protein kinase alpha- (AMPKα-) acetyl CoA carboxylase (ACC) axis. Further investigation of cotreatment of VN with the AMPK agonist AICAR or AMPK inhibitor Compound C showed that VN can activate the phosphorylation of AMPKα in compensation to the inhibition of Compound C. In conclusion, VN shows antiobesity effects in HFD-induced obese C57BL/6J mice. In 3T3-L1 adipocytes, VN has antiadipogenic features, which is due to activating the LKB1-AMPKα-ACC axis. These results suggest that VN has a potential benefit in preventing obesity.

10.
Am J Chin Med ; 44(3): 565-78, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27109161

RESUMO

Rutin, also called rutoside or quercetin-3-O-rutinoside and sophorin, is a glycoside between the flavonol quercetin and the disaccharide rutinose. Although many effects of rutin have been reported in vitro and in vivo, the anti-adipogenic effects of rutin have not been fully reported. The aim of this study was to confirm how rutin regulates adipocyte related factors. In this study, rutin decreased the expressions of adipogenesis-related genes, including peroxisome proliferators, activated receptor [Formula: see text] (PPAR[Formula: see text], CCAAT/enhancer-binding protein [Formula: see text] (C/EBP[Formula: see text], fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase in 3T3-L1 cells. Rutin also repressed the expression of lipin1, which is an upstream regulator that controls PPAR[Formula: see text] and C/EBP[Formula: see text]. In addition, when 3T3-L1 was transfected with lipin1 siRNA to block lipin1 function, rutin did not affect the expressions of PPAR[Formula: see text] and C/EBP[Formula: see text]. These results suggest that rutin has an anti-adipogenic effect that acts through the suppression of lipin1, as well as PPAR[Formula: see text] and C/EBP[Formula: see text].


Assuntos
Adipogenia/efeitos dos fármacos , Adipogenia/genética , Proteínas Nucleares/fisiologia , Fosfatidato Fosfatase/fisiologia , Rutina/farmacologia , Células 3T3 , Proteínas Quinases Ativadas por AMP/fisiologia , Animais , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Camundongos , Proteínas Nucleares/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , Fosfatidato Fosfatase/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
11.
J Cell Biochem ; 117(9): 2067-77, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26852013

RESUMO

Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Furanos/farmacologia , Lignanas/farmacologia , Obesidade , Perda de Peso/efeitos dos fármacos , Células 3T3-L1 , Animais , Gorduras na Dieta/farmacologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo
12.
BMC Complement Altern Med ; 15: 196, 2015 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-26104582

RESUMO

BACKGROUND: Ixeris dentata Nakai has been used for the treatment of mithridatism, calculous, indigestion, pneumonia, hepatitis, and tumors in Korea, China, and Japan. However, the effect of a water extract of Ixeris dentata (ID) and its molecular mechanism on allergic inflammation has not been elucidated. In this study, we attempted to evaluate the effects of ID and its major compound caffeic acid on allergic inflammation in vivo and in vitro. METHODS: ID was applied to 2, 4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD)-like skin lesion mice and immune cell infiltration, cytokine production, and the activation of mitogen-activated protein kinases (MAPKs) were investigated. Moreover, the effect of ID on compound 48/80-induced anaphylactic shock was investigated in a mouse model. The human keratinocyte cell line (HaCaT cells) and human mast cells (HMC-1) were treated with ID or caffeic acid to investigate the effects on the production of chemokines and proinflammatory cytokines and on the activation of MAPKs. RESULTS: ID inhibited the serum levels of IgE and interleukin (IL)-1ß in DNFB-induced AD-like skin lesion mouse models and suppressed anaphylactic shock in the mouse models. ID and caffeic acid inhibited the production of chemokines and adhesion molecules in HaCaT cells. In addition, ID reduced the release of tumor necrosis factor-α and IL-8 via the inhibition of MAPKs phosphorylation in HMC-1 cells. CONCLUSIONS: These results suggest that ID is a potential therapeutic agent for allergic inflammatory diseases, including dermatitis.


Assuntos
Asteraceae/química , Ácidos Cafeicos/farmacologia , Inflamação/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais , Animais , Linhagem Celular , Humanos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
13.
Am J Chin Med ; 43(4): 731-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26119957

RESUMO

In this study, we found that alpha-pinene (α-pinene) exhibits anti-inflammatory activity through the suppression of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) pathway in mouse peritoneal macrophages. α-Pinene is found in the oils of many coniferous trees and rosemary. We investigated the inhibitory effects of α-Pinene on inflammatory responses induced by lipopolysaccharide (LPS) using mouse peritoneal macrophages. α-Pinene significantly decreased the LPS-induced production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). α-Pinene also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-stimulated macrophages. Additionally, the activations of MAPKs and NF-κB were attenuated by means of α-pinene treatment. These results indicate that α-pinene has an anti-inflammatory effect and that it is a potential candidate as a new drug to treat various inflammatory diseases.


Assuntos
Anti-Inflamatórios , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Macrófagos Peritoneais/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monoterpenos/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Monoterpenos Bicíclicos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Depressão Química , Inflamação/tratamento farmacológico , Inflamação/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/antagonistas & inibidores , Masculino , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular , Monoterpenos/uso terapêutico , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Mol Med Rep ; 12(3): 3549-3556, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26005209

RESUMO

Ulcerative colitis (UC) is a type of inflammatory bowel disease and is considered a chronic gastrointestinal disorder. Igongsan (IGS) is a Korean herbal medicine, which has been used to treat digestive disorders. However, the ameliorative effect and molecular mechanisms of IGS in intestinal inflammation have not yet been studied in detail. The present study aimed to investigate the protective effects of IGS and its constituent, ergosterol, in a mouse model of dextran sulfate sodium (DSS)­induced colitis. Colitis was induced in mice by supplementing their drinking water with 5% (w/v) DSS for 7 days. The effects of IGS were then determined on DSS­induced clinical signs of colitis, including weight loss, colon shortening, diarrhea and obscure/gross bleeding. In addition, the effects of IGS were determined on the expression levels of inflammation­associated genes in the colon tissue of DSS­treated mice. The results of the present study demonstrated that mice treated with DSS exhibited marked clinical symptoms, including weight loss and reduced colon length. Treatment with IGS attenuated these symptoms and also suppressed the expression levels of tumor necrosis factor­α and interleukin­6, as well as the expression of cyclooxygenase­2 in the colon tissue of DSS­treated mice. IGS also reduced the activation of the transcription factor nuclear factor­κB p65 in the colon tissue of DSS­treated mice. In addition, ergosterol was shown to attenuate the DSS­induced clinical symptoms of colitis in mice. In conclusion, the present study provided experimental evidence that IGS may be a useful therapeutic drug for patients with UC.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Sulfato de Dextrana , Ergosterol/uso terapêutico , Animais , Anti-Inflamatórios/química , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/patologia , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/imunologia , Dinoprostona/análise , Dinoprostona/imunologia , Ergosterol/química , Feminino , Interleucina-6/análise , Interleucina-6/imunologia , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/análise , NF-kappa B/imunologia , Plantas Medicinais/química , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologia
15.
Mol Med Rep ; 12(1): 315-22, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25738645

RESUMO

Cisplatin is an effective anti-cancer drug; however, one of its side effects is irreversible sensorineural hearing damage. Korean Red Ginseng (KRG) has been used clinically for the treatment of various diseases; however, the underlying mechanism of KRG treatment of ototoxicity has not been studied extensively. The present study aimed to further investigate the mechanism of KRG on cisplatin-induced toxicity in auditory HEI-OC1 cells in vitro, as well as in vivo. The pharmacological effects of KRG on cisplatin-induced changes in the hearing threshold of mice were determined, as well as the effect on the impairment of hair cell arrays. In addition, in order to elucidate the protective mechanisms of KRG, the regulatory effects of KRG on cisplatin-induced apoptosis-associated gene levels and nuclear factor-κB (NF-κB) activation were investigated in auditory cells. The results revealed that KRG prevented cisplatin-induced alterations in the hearing threshold of mice as well as the destruction of hair cell arrays in rat organ of Corti primary explants. In addition, KRG inhibited cisplatin-mediated cell toxicity, reactive oxygen species generation, interleukin-6 production, cytochrome c release and activation of caspases-3 in the HEI-OC1 auditory cell line. Furthermore, the results demonstrated that KRG inhibited the activation of NF-κB and caspase-1. In conclusion, these results provided a model for the pharmacological mechanism of KRG and provided evidence for potential therapies against ototoxicity.


Assuntos
Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cisplatino/toxicidade , Panax/química , Extratos Vegetais/farmacologia , Animais , Caspase 1/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Citocromos c/metabolismo , Ativação Enzimática/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Células Ciliadas Auditivas/citologia , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Órgão Espiral/efeitos dos fármacos , Órgão Espiral/patologia , Panax/metabolismo , Extratos Vegetais/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , República da Coreia
16.
J Craniomaxillofac Surg ; 43(3): 342-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25648068

RESUMO

INTRODUCTION: Functional overloading can lead to disc displacement in the temporomandibular joint (TMJ), and a high incidence of disc displacement has been reported in patients with facial asymmetry. The aim of this study was to assess the dynamic condylar movement in patients (n = 26) with facial asymmetry using a simulation system with 3-dimensional computed tomographic images and tracking camera system. MATERIAL AND METHODS: The intra-articular distance (IAD) between the condyle and glenoid fossa was recorded during TMJ movement as a parameter for functional overloading and compared between Group I with severe asymmetry and Group II with mild asymmetry. RESULTS: The average IAD was shorter in Group I than Group II, especially at the lowest point (P < 0.05). The ratio of IAD narrowing in Group I was significantly larger than in Group II (P < 0.05). The mean IAD were slightly smaller on the deviated side (3.41 mm) than on the nondeviated side (3.55 mm) in Group I, even though there was no statistical significance. The maximum displacement in Group I was longer than in Group II and had no significant difference between deviated side and nondeviated side. CONCLUSION: We suggested that the reduced IAD resulting from TMJ overloading can lead to internal derangement in severe facial asymmetry.


Assuntos
Assimetria Facial/fisiopatologia , Côndilo Mandibular/patologia , Amplitude de Movimento Articular/fisiologia , Osso Temporal/patologia , Articulação Temporomandibular/patologia , Adulto , Algoritmos , Fenômenos Biomecânicos , Cefalometria/métodos , Simulação por Computador , Assimetria Facial/classificação , Feminino , Marcadores Fiduciais , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Luxações Articulares/patologia , Luxações Articulares/fisiopatologia , Masculino , Côndilo Mandibular/fisiopatologia , Fotografação/métodos , Estresse Mecânico , Articulação Temporomandibular/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Interface Usuário-Computador , Adulto Jovem
17.
J Craniomaxillofac Surg ; 42(8): 2010-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25458350

RESUMO

Accurate surgical planning and transfer of the planning in orthognathic surgery are very important in achieving a successful surgical outcome with appropriate improvement. Conventionally, the paper surgery is performed based on a 2D cephalometric radiograph, and the results are expressed using cast models and an articulator. We developed an integrated orthognathic surgery system with 3D virtual planning and image-guided transfer. The maxillary surgery of orthognathic patients was planned virtually, and the planning results were transferred to the cast model by image guidance. During virtual planning, the displacement of the reference points was confirmed by the displacement from conventional paper surgery at each procedure. The results of virtual surgery were transferred to the physical cast models directly through image guidance. The root mean square (RMS) difference between virtual surgery and conventional model surgery was 0.75 ± 0.51 mm for 12 patients. The RMS difference between virtual surgery and image-guidance results was 0.78 ± 0.52 mm, which showed no significant difference from the difference of conventional model surgery. The image-guided orthognathic surgery system integrated with virtual planning will replace physical model surgical planning and enable transfer of the virtual planning directly without the need for an intermediate splint.


Assuntos
Procedimentos Cirúrgicos Ortognáticos/métodos , Planejamento de Assistência ao Paciente , Cirurgia Assistida por Computador/métodos , Interface Usuário-Computador , Adulto , Algoritmos , Pontos de Referência Anatômicos/anatomia & histologia , Gráficos por Computador , Simulação por Computador , Articuladores Dentários , Feminino , Marcadores Fiduciais , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Registro da Relação Maxilomandibular/instrumentação , Masculino , Maxila/cirurgia , Modelos Anatômicos , Tomografia Computadorizada Multidetectores/métodos , Rotação , Contenções , Adulto Jovem
18.
Colloids Surf B Biointerfaces ; 123: 838-44, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25454753

RESUMO

In bone tissue engineering, scaffolds have been investigated for their ability to support osteoblast growth and differentiation for recovery of damaged bones. Tunicate cellulose nanowhisker (CNW) film and mechanical strain were assessed for their suitability for osteoblasts. In this study, sulfuric acid hydrolysis extraction of tunicates integuments was conducted to obtain CNWs, which were found to be acceptable for adhering, growing, and differentiating osteoblasts without cytotoxicity. Mechanical stress enhanced osteoblast differentiation, and cell survival rate was recovered at around day 3, although there was a slight increase in cell death at day 1 after stimulation. We also found that intracellular flux of calcium ion was related to increased differentiation of CNWs under mechanical stress. Overall, we demonstrated the suitability of tunicate CNWs as a scaffold for bone tissue engineering and developed a complex system based on CNW for osteoblast growth and differentiation that will be useful for bone substitute fabrication.


Assuntos
Osso e Ossos/citologia , Celulose/química , Nanoestruturas/química , Osteoblastos/citologia , Cálcio/química , Estresse Mecânico , Engenharia Tecidual/métodos
19.
J Craniomaxillofac Surg ; 42(7): 1315-21, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24780355

RESUMO

We developed a new method to record and reproduce the three-dimensional natural head position (NHP) from a single photograph of a patient's face using a pose from orthography and scaling with iterations (POSIT) algorithm. We attached 4-mm spherical ceramic markers to the patient's face as feature points. A frontal photograph of the patient's NHP was taken using an ordinary digital camera parallel to the global horizon. Computed tomography (CT) was then performed on the patient with the markers. The ceramic marker positions were determined in the 2D image and corresponded to points in the 3D model. The 3D rotation matrix determined using the feature points via the POSIT method was applied to the CT model to reproduce the NHP. A skull phantom was used to evaluate the accuracy and reproducibility of the developed method. The degree difference (°) between the true and POSIT orientations in the roll, pitch, and yaw directions was quantified as the error. The mean accuracy was -0.04 ± 0.15°, -0.17 ± 0.50°, and -0.02 ± 0.37° in the roll, pitch, and yaw directions, respectively. The method developed was highly reproducible during intra-observer and inter-observer variation analyses. The accuracy of the method was clinically acceptable, and the procedure was time- and cost-effective. This method is accurate and inexpensive; additionally, it does not affect the patient's lip position, and we expect it to be routinely used during orthognathic surgery.


Assuntos
Algoritmos , Cabeça/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Fotografação/métodos , Tomografia Computadorizada por Raios X/métodos , Cerâmica/química , Marcadores Fiduciais , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Imageamento Tridimensional/estatística & dados numéricos , Variações Dependentes do Observador , Imagens de Fantasmas , Fotografação/estatística & dados numéricos , Reprodutibilidade dos Testes , Rotação , Tomografia Computadorizada por Raios X/estatística & dados numéricos
20.
Med Eng Phys ; 36(6): 715-20, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24378382

RESUMO

PURPOSE: We compared implant stability as determined by the peak frequency from the impact response with the implant stability quotient (ISQ) by resonance frequency analysis (RFA) in various artificial bone conditions. The clinical bone conditions were simulated using an artificial bone material with different cortical thicknesses and trabecular densities. MATERIALS AND METHODS: The artificial bone material was solid, rigid polyurethane. The polyurethane foam of 0.8g/cm(3) density was used for the cortical bone layer, and that of 0.08, 0.16, 0.24, 0.32, and 0.48g/cm(3) densities for the trabecular bone layer. The cortical bone material of 4 different thicknesses (1.4, 1.6, 1.8, and 2.0mm) was attached to the trabecular bone with varying density. Two types of dental implants (10 and 13mm lengths of 4.0mm diameter) were placed into the artificial bone blocks. An inductive sensor was used to measure the vibration caused by tapping the adapter-implant assembly. The peak frequency of the power spectrum of the impact response was used as the criterion for implant stability. The ISQ value was also measured for the same conditions. RESULTS: The stability, as measured by peak frequency (SPF) and ISQ value, increased as the trabecular density and the cortical density increased in linear regression analysis. The SPF and ISQ values were highly correlated with each other when the trabecular bone density and cortical bone thickness changed (Pearson correlation=0.90, p<0.01). The linear regression of the SPF with the cortical bone thickness showed higher goodness of fit (R(2) measure) than the ISQ value with the cortical bone thickness. The SPF could differentiate implantation conditions as many as the ISQ value when the trabecular bone density and the cortical density changed. However, the ISQ value was not consistent with the general stability tendency in some conditions. CONCLUSION: The SPF showed better consistency and differentiability with implant stability than the ISQ value by resonance frequency analysis in the various implantation conditions.


Assuntos
Substitutos Ósseos , Osso e Ossos , Implantes Dentários , Vibração , Densidade Óssea , Osso e Ossos/fisiologia , Análise do Estresse Dentário , Análise de Falha de Equipamento , Humanos , Modelos Lineares , Poliuretanos
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