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1.
Molecules ; 25(9)2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32349276

RESUMO

Pancreatic cancer (PC) is one of the most severe cancers, and its incidence and mortality rates have steadily increased in the past decade. In this study, we demonstrate the effect of Angelica gigas Nakai extract on pancreatic ductal adenocarcinoma cells. We prepared A. gigas Nakai ethanol extract (AGE) using roots of A. gigas Nakai and detected its active compound decursin from AGE by ultra-performance liquid chromatography analysis. AGE and decursin significantly decreased viability and colony formation of PANC-1 and MIA PaCa-2 cells. AGE and decursin induced G0/G1 phase arrest through downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). Caspase-3-dependent apoptosis of PANC-1 cells was promoted by AGE and decursin. Additionally, nontoxic concentrations of AGE and decursin treatment could suppress matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity by inhibiting p38 phosphorylation. Taken together, this study demonstrates that AGE and decursin have potential properties to be considered in PC treatment.

2.
Phytomedicine ; 68: 153147, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32028184

RESUMO

BACKGROUND: Gomisin A (G.A), a lignan compound extracted from the fruits of Schisandra chinensis, is known to exert anti-tumor effects on hepatocarcinoma and colorectal cancer cells. Suppression of proliferation and metastatic abilities of cancer cells are some effective cancer treatment methods. PURPOSE: The objective of this study is to investigate the effects of G.A on metastatic melanoma, and the mechanism by which it affects metastatic melanoma. STUDY DESIGN: The anti-proliferative and anti-metastatic effects of G.A were observed in in vitro and in vivo. METHODS: WST assay and flow cytometry were conducted to investigate the effect of G.A on proliferation, cell cycle arrest, and apoptosis in metastatic melanoma cell lines. Migration and invasion abilities of G.A-treated melanoma cells were observed by wound healing and invasion assays. RESULTS: G.A (25-100 µM) decreased the viability of melanoma cells by inducing cell cycle arrest and apoptosis. These anti-proliferative effects of G.A were found to be mediated by AMPK, ERK, and JNK activation. G.A (5-20 µM) decreased the migration and invasion of melanoma cells by suppressing epithelial-mesenchymal transition (EMT). Consequently, G.A (2-50 mg/kg) inhibited lung metastasis by suppressing EMT and inducing cell cycle arrest and apoptosis in melanoma cells. CONCLUSION: These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Lignanas/farmacologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , MAP Quinase Quinase 4/metabolismo , Melanoma/metabolismo , Camundongos Endogâmicos C57BL , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Mol Med Rep ; 21(1): 258-266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746359

RESUMO

The major role of inner medullary collecting duct (IMCD) cells is to maintain water and sodium homeostasis. In addition to the major role, it also participates in the protection of renal and systemic inflammation. Although IMCD cells could take part in renal and systemic inflammation, investigations on renal inflammation in IMCD cells have rarely been reported. Although berberine (BBR) has been reported to show diverse pharmacological effects, its anti­inflammatory and protective effects on IMCD cells have not been studied. Therefore, in the present study, we examined the anti­inflammatory and protective effects of BBR in mouse IMCD­3 (mIMCD­3) cells against lipopolysaccharide (LPS). An MTT assay was carried out to investigate the toxicity of BBR on mIMCD­3 cells. Reverse transcription quantitative­PCR and western blotting were performed to analysis pro­inflammatory molecules and cytokines. Mechanisms of BBR were examined by western blotting and immunocytochemistry. According to previous studies, pro­inflammatory molecules, such as inducible nitric oxide synthase and cyclooxygenase­2, and pro­inflammatory cytokines, such as interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α are increased in LPS­exposed mIMCD­3 cells. However, the production of these pro­inflammatory molecules is significantly inhibited by treatment with BBR. In addition, BBR inhibited translocation of nuclear factor (NF)­κB p65 from the cytosol to the nucleus, and degradation of inhibitory κ­Bα in LPS­exposed mIMCD­3 cells. In conclusion, BBR could inhibit renal inflammatory responses via inhibition of NF­κB signaling and ultimately contribute to amelioration of renal injury during systemic inflammation.

4.
J Craniofac Surg ; 31(1): e103-e107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31842069

RESUMO

OBJECTIVE: Cranioplasty is essential because cranial defects cause cosmetic and functional problems, and neurologic sequalae in patients. However, reconstruction options are limited in patients with unfavorable conditions. This study aimed to review our experience with skull defect reconstruction using autogenous bone with sagittal split rib bone grafts or latissimus dorsi rib myoosseocutaneous free flaps. METHODS: Patients who underwent autogenous bone graft for cranial defect coverage from December 2011 to November 2015 at our institution were reviewed. Rib bone graft or latissimus dorsi rib myoosseocutaneous free flaps were done to cover the defect. The patient follow-up period ranged from 3 months to 7 years. RESULTS: There were 6 patients, with 9 surgeries. Two cases of latissimus dorsi rib myoosseocutaneous free flap procedures were performed in 2 patients and 7 sagittal split rib bone grafts were performed in 6 patients. There were no postoperative infections in any patients, despite 4 patients had previous surgical site infection histories. Two patients with neurologic sequalae showed improvement after the surgeries. CONCLUSION: Sagittal split rib bone graft and latissimus dorsi rib myoosseocutaneous free flap procedures could be fine options for calvarial reconstruction of defects under the unfavorable conditions of bilateral cranial defects or previous infection history.


Assuntos
Retalhos de Tecido Biológico/cirurgia , Costelas/transplante , Crânio/cirurgia , Músculos Superficiais do Dorso/transplante , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Reconstrutivos , Transplante Autólogo
5.
Plast Reconstr Surg ; 144(1): 9e-17e, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246795

RESUMO

BACKGROUND: A closed-suction drain is usually inserted during tissue expander-based breast reconstruction. Prolonged duration of drain retention can disturb patients' daily lives and affect overall sociomedical costs. This study aimed to investigate factors that may influence the drainage and to identify predictors of unusually prolonged drain duration. METHODS: Patients who underwent delayed-immediate, two-stage breast reconstruction using a tissue expander between January of 2013 and July of 2017 were reviewed. Prolonged drain duration was defined as drain duration for longer than the 75th percentile of that for the entire cohort. Effects of patient- and operation-related variables on drainage and prolonged drain duration were evaluated. RESULTS: A total of 1056 cases (1002 patients) were analyzed. The median drain duration was 10 days. Drain placement for more than 12 postoperative days was observed in 256 cases (24.2 percent), classified as prolonged drain duration. Multivariate analyses demonstrated that old age, high body mass index, neoadjuvant chemotherapy, insertion of large Siltex textured tissue expanders, and greater volume of initial inflation were independent risk factors of prolonged drain duration. The size and texture of the tissue expanders and initial inflation volume retained their influence, regardless of mastectomy specimen weight. Use of acellular dermal matrix had contradictory effects according to breast size, being protective against prolonged drain duration in cases with mastectomy specimen weight greater than 400 g, and being a significant predictor for it in cases with mastectomy specimen weight less than or equal to 400 g. CONCLUSION: Several factors, including reconstructive operation-related factors, might influence drain duration following tissue expander-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Assuntos
Neoplasias da Mama/cirurgia , Drenagem/estatística & dados numéricos , Mamoplastia/efeitos adversos , Expansão de Tecido/efeitos adversos , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Mama/patologia , Neoplasias da Mama/patologia , Remoção de Dispositivo/estatística & dados numéricos , Feminino , Humanos , Mamoplastia/instrumentação , Mamoplastia/métodos , Mastectomia/métodos , Pessoa de Meia-Idade , Tamanho do Órgão , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Expansão de Tecido/instrumentação , Dispositivos para Expansão de Tecidos/efeitos adversos , Adulto Jovem
6.
Chin J Integr Med ; 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31069694

RESUMO

OBJECTIVE: To study the effect of Liuwei Dihuang Decoction () or Yukmijihwangtang (YJT) on endurance exercise by in vivo experiment. METHODS: ICR mice were randomly divided into the control group (distilled water) and the YJT groups (1, 10, 100 mg/kg), 5 animals per group. YJT and distilled water were orally administered. The anti-fatigue effect of YJT was evaluated by open fifiled test (OFT), forced swimming test (FST), and tail suspension test (TST). RESULTS: In the OFT, YJT signifificantly increased the total movement distance in a dose-dependent manner. Additionally, treatment with YJT signifificantly decreased immobility time in the FST and the TST. Various neurotransmitters such as norepinephrine (NE), serotonin (5-HT), dopamine (DA) levels were increased by FST. Administration of YJT down-regulated the expression levels of NE, 5-HT, 5-hydroxyindole-acetic acid (5-HIAA), and DA in the brain stem and hypothalamus of mice. Moreover, protein expression of HSP70 in mice liver and heart muscles was signifificantly increased in the YJT groups. CONCLUSIONS: YJT could ameliorate fatigue and enhance exercise tolerance through suppressing of brain monoamines including NE, 5-HT, 5-HIAA, and DA in FST mice model.

7.
Phytomedicine ; 62: 152952, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132754

RESUMO

BACKGROUND: Although rubrofusarin-6-ß-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated. PURPOSE: The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG. STUDY DESIGN: In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model. METHODS: We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis. RESULTS: RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), peroxisome proliferator-activated receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver. CONCLUSION: RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Cromonas/farmacologia , Glucosídeos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipogenia/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Serina-Treonina Quinases TOR/metabolismo
8.
J Ginseng Res ; 43(2): 282-290, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30976166

RESUMO

Background: Ginsenoside Rg3 (G-Rg3) is the major bioactive ingredient of Panax ginseng and has many pharmacological effects, including antiadipogenic, antiviral, and anticancer effects. However, the effect of G-Rg3 on mast cell-mediated allergic inflammation has not been investigated. Method: The antiallergic effects of G-Rg3 on allergic inflammation were evaluated using the human and rat mast cell lines HMC-1 and RBL-2H3. Antiallergic effects of G-Rg3 were detected by measuring cyclic adenosine monophosphate (cAMP), detecting calcium influx, and using real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and in vivo experiments. Results: G-Rg3 decreased histamine release from activated mast cells by enhancing cAMP levels and calcium influx. Proinflammatory cytokine production was suppressed by G-Rg3 treatment via regulation of the mitogen-activated protein kinases/nuclear factor-kappa B and receptor-interacting protein kinase 2 (RIP2)/caspase-1 signaling pathway in mast cells. Moreover, G-Rg3 protected mice against the IgE-mediated passive cutaneous anaphylaxis reaction and compound 48/80-induced anaphylactic shock. Conclusion: G-Rg3 may serve as an alternative therapeutic agent for improving allergic inflammatory disorders.

9.
J Ginseng Res ; 43(1): 68-76, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30662295

RESUMO

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-ß1 (TGF-ß1)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-ß1-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-ß1-induced EMT via TGF-ß1/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

10.
Oncol Rep ; 41(1): 202-212, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30365120

RESUMO

Galla Rhois is a commonly used medicine in East Asia for the treatment of several diseases. However, the effects of Galla Rhois on the metastasis of colorectal cancer (CRC) and the underlying molecular mechanisms have not been studied. We investigated the anti­metastatic properties of Galla Rhois water extract (GRWE) on metastatic CRC cells. The effect of GRWE on the viability of colon 26 (CT26) cells was evaluated using WST­8 assay. Annexin V assay and western blot analysis were performed to elucidate the underlying molecular mechanisms involved in apoptosis. GRWE suppressed viability of CT26 cells by inducing apoptosis through the cleavage of caspase­3 and PARP, downregulation of caspase­8, caspase­9, Bcl­2 and Bcl­xL, and upregulation of Bax. Metastatic phenotypes such as epithelial­mesenchymal transition (EMT), migration, and invasion of CRC cells were investigated by real­time reverse transcription polymerase chain reaction, wound healing assay, and matrigel invasion assay, respectively. Non­cytotoxic concentrations of GRWE inhibited EMT in CRC cells by regulating the expression of EMT markers. GRWE attenuated cell migration and invasion through the inhibition of matrix metalloproteinase (MMP)­2 and MMP­9 activity. Moreover, GRWE suppressed colorectal lung metastasis in vivo, suggestive of its potential application for the treatment of colorectal metastasis.


Assuntos
Adenilato Quinase/metabolismo , Produtos Biológicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Animais , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Nutrients ; 12(1)2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31887988

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the diseases with high prevalence and mortality worldwide. In particular, metastatic CRC shows low probability of surgery and lacks proper treatment. In this study, we conducted experiments to investigate the inhibitory effect of betulin against metastatic CRC and related mechanisms. METHODS: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin. RESULTS: betulin decreased viability of metastatic CRC cells, including CT26, HCT116, and SW620 cell lines. Through PI3K/Akt/mTOR inactivation, betulin induced AMPK-mediated G0/G1 phase arrest and autophagy of CT26 and HCT116 cells. In addition, betulin occurred caspase-dependent apoptosis via the mitogen-activated protein kinase signaling pathway in metastatic CRC cells. Moreover, orally administered betulin significantly inhibited metastasis of CT26 cells to the lung. CONCLUSION: Our results demonstrate the anti-metastatic effect and therapeutic potential of betulin in metastatic CRC treatment.

12.
Front Pharmacol ; 9: 986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210348

RESUMO

Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial-mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC.

13.
J Ethnopharmacol ; 220: 177-187, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29601980

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The pharmacological effect derived from herb-herb interaction is important to constitute the prescription especially in traditional oriental medicine. The relationship of two medicinal herbs is called "couplet medicinals" which is used in pair for the purpose of enhancing the therapeutic effect, reducing the toxic effect or the adverse effect. The "Eighteen Incompatible Medicaments" constitute one of the contents in the incompatibility of traditional oriental drugs in a prescription. Among the "Eighteen Incompatible Medicaments", the roots and rhizomes of Veratrum nigrum (VN), is incompatible with the roots and rhizomes of Panax ginseng (PG). However, definite evidences of adverse effect by these combinations has yet to be reported. MATERIALS AND METHODS: The aim of the present study was to investigate the effects of ethanol extracts of PG, VN, and their combination (P + V) on the metastatic ability of colorectal cancer (CRC) cells using WST assay, flow cytometry, western blot analysis, real-time RT-PCR, immunofluorescence, migration assay, invasion assay, zymography, and an in vivo experiment with a lung-metastasis mouse model. RESULTS: The PG extract decreased cell proliferation by inducing cell cycle arrest and apoptosis of CRC cells. In addition, PG inhibited metastatic abilities of CRC cells including Epithelial-Mesenchymal Transition, migration, and invasion. Additionally, the PG extract suppressed lung metastasis of the CRC cells in the mouse model. However, the P + V extract exhibited weaker anti-proliferative and anti-metastatic effects than PG alone. CONCLUSION: Based on these results, the P + V couplet medicinal attenuates the anti-metastatic effects of PG, both in vitro and in vivo.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Veratrum/química , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Raízes de Plantas , Rizoma
14.
Front Pharmacol ; 9: 68, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29459827

RESUMO

Rosmarinic acid (RA) has been used as an anti-inflammatory, anti-diabetic, and anti-cancer agent. Although RA has also been shown to exert an anti-metastatic effect, the mechanism of this effect has not been reported to be associated with AMP-activated protein kinase (AMPK). The aim of this study was to elucidate whether RA could inhibit the metastatic properties of colorectal cancer (CRC) cells via the phosphorylation of AMPK. RA inhibited the proliferation of CRC cells through the induction of cell cycle arrest and apoptosis. In several metastatic phenotypes of CRC cells, RA regulated epithelial-mesenchymal transition (EMT) through the upregulation of an epithelial marker, E-cadherin, and the downregulation of the mesenchymal markers, N-cadherin, snail, twist, vimentin, and slug. Invasion and migration of CRC cells were inhibited and expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were decreased by RA treatment. Adhesion and adhesion molecules such as ICAM-1 and integrin ß1 expressions were also reduced by RA treatment. In particular, the effects of RA on EMT and MMPs expressions were due to the activation of AMPK. Moreover, RA inhibited lung metastasis of CRC cells by activating AMPK in mouse model. Collectively, these results proved that RA could be potential therapeutic agent against metastasis of CRC.

15.
J Agric Food Chem ; 65(43): 9443-9452, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28976750

RESUMO

The Arctium lappa seeds (Arctii Fructus) and its major active compound, arctigenin (ARC), are known to have anticancer, antiobesity, antiosteoporosis, and anti-inflammatory activities. However, the effect of Arctii Fructus and ARC on mast cell-mediated allergic inflammation and its associated mechanism have not been elucidated. Therefore, we attempted to investigate the antiallergic activity of Arctii Fructus and ARC on mast cells and experimental mouse models. Arctii Fructus water extract (AFW) or ethanol extract (AFE) and ARC reduced the production of histamine and pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, IL-8, and TNF-α in mast cells. AFW, AFE, and ARC inhibited phosphorylation of MAPKs and NF-κB in activated mast cells. Moreover, IgE-mediated passive cutaneous anaphylaxis and compound 48/80-induced anaphylactic shock were suppressed by AFW, AFE, and ARC administration. These results suggest that Arctii Fructus and ARC are potential therapeutic agents against allergic inflammatory diseases.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/administração & dosagem , Arctium/química , Furanos/administração & dosagem , Lignanas/administração & dosagem , Mastócitos/imunologia , Extratos Vegetais/administração & dosagem , Anafilaxia/genética , Anafilaxia/imunologia , Animais , Antialérgicos/química , Furanos/análise , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Lignanas/análise , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
16.
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
17.
Metabolism ; 73: 85-99, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28732574

RESUMO

OBJECTIVE: Brown adipose tissue (BAT) activation has been identified as a possible target to treat obesity and to protect against metabolic diseases by increasing energy consumption. We explored whether albiflorin (AF), a natural compound, could contribute to lowering the high risk of obesity with BAT and primary brown preadipocytes in vivo and in vitro. MATERIALS/METHODS: Human adipose tissue-derived mesenchymal stem cells (hAMSCs) were cultured with adipogenic differentiation media with or without AF. Male C57BL/6J mice (n=5 per group) were fed a high-fat diet (HFD) for six weeks with or without AF. Brown preadipocytes from the interscapular BAT of mice were cultured with or without AF. RESULTS: In white adipogenic differentiation of hAMSCs, AF treatment significantly reduced the formation of lipid droplets and the expression of adipogenesis-related genes. In HFD-induced obese C57BL/6J mice, AF treatment significantly reduced body weight gain as well as the weights of the white adipose tissue, liver and spleen. Furthermore, AF induced the expression of genes involved in thermogenic function in BAT. In primary brown adipocytes, AF effectively stimulated the expressions of thermogenic genes and markedly up-regulated the AMP-activated protein kinase (AMPK) signaling pathway. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 nullified the induction of the thermogenic genes by AF in primary brown adipocytes. Moreover, AF activated beige cell marker genes induced by the pharmacological activation of peroxisome proliferator-activated receptor γ in hAMSCs. CONCLUSION: This study shows that AF prevents the development of obesity in hAMSCs and mice fed an HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes by AMPK and PI3K/AKT.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Células-Tronco Mesenquimais/citologia , Obesidade/tratamento farmacológico , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Termogênese/genética , Adipócitos Marrons/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Diferenciação Celular , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ativação Transcricional
18.
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
19.
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
20.
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.

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