RESUMO
BACKGROUND: Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing. METHODS: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors. RESULTS: On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited the most consistent increase of expression, while also CXC chemokine ligand 2 (CXCL2), Interleukin8 (IL8) and bone morphogenetic protein (BMP2) were slightly up-regulated, suggesting a positive influence of A. montana on neutrophil recruitment and on angiogenesis. MMP1, coding for a metalloproteinase capable of cleaving extracellular matrix substrates, was down-regulated. Most results showed non-linearity of the dose-effect relationship. CONCLUSIONS: This exploratory study provides new insights into the cellular and molecular mechanisms of action of A. montana as a promoter of healing, since some of the genes it modifies are key regulators of tissue remodelling, inflammation and chemotaxis.
Assuntos
Arnica , Citocinas/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cicatrização , Citocinas/genética , Regulação da Expressão Gênica , Homeopatia , Humanos , Fitoterapia , Extratos Vegetais/administração & dosagem , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Increasing evidence suggests that the inability to undergo apoptosis is an important factor in the development and progression of prostate cancer. Agents that induce apoptosis may inhibit tumor growth and provide therapeutic benefit. In a recent study, the authors found that certain homeopathic treatments produced anticancer effects in an animal model. In this study, the authors examined the immunomodulating and apoptotic effects of these remedies. MATERIALS AND METHODS: The authors investigated the effect of a homeopathic treatment regimen containing Conium maculatum, Sabal serrulata, Thuja occidentalis, and a MAT-LyLu Carcinosin nosode on the expression of cytokines and genes that regulate apoptosis. This was assessed in prostate cancer tissues, extracted from animals responsive to these drugs, using ribonuclease protection assay or reverse transcription polymerase chain reaction. RESULTS: There were no significant changes in mRNA levels of the apoptotic genes bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, FasL, or the cytokines interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-beta, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-alpha, IL-2, and interferon-gamma in prostate tumor and lung metastasis after treatment with homeopathic medicines. CONCLUSIONS: This study indicates that treatment with the highly diluted homeopathic remedies does not alter the gene expression in primary prostate tumors or in lung metastasis. The therapeutic effect of homeopathic treatments observed in the in vivo experiments cannot be explained by mechanisms based on distinct alterations in gene expression related to apoptosis or cytokines. Future research should explore subtle modulations in the expression of multiple genes in different biological pathways.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Homeopatia , Fitoterapia , Neoplasias da Próstata/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Citocinas/genética , Modelos Animais de Doenças , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To examine the efficacy of saenghyuldan and its components, Ginseng Radix, Paeoniae Radix Alba, and Hominis Placenta extracts (SHD, GR, PRA, and HP, respectively) on the hemopoiesis in a myelosuppression model system. METHODS: Susceptibility to cyclophosphamide (CP) and S180 carcinoma was determined in SHD, GR, PRA, and HP-treated mice. Analysis of peripheral blood and bone marrow cells was demonstrated by changes in cell types and histopathologic examination. The expression of cytokine mRNAs involved in hemopoiesis was examined by RT-PCR. RESULTS: SHD and its separated components (GR, HP, and PRA, respectively) significantly increased the survival in CP- and S180-treated mice. The hematology data demonstrated that all the agents augmented monocyte and leucocyte counts in the peripheral blood and increased bone marrow density and the ratio of leukocyte to erythrocyte in the bone marrow. These findings were positively correlated with the up-regulation of cytokine mRNA expression such as granulocyte colony-stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO), stem cell factor (SCF), and c-Kit. CONCLUSION: SHD is an effective remedy for the bone marrow failure and myelosuppression occurring during chemotherapy.
Assuntos
Hematopoese/efeitos dos fármacos , Materia Medica/farmacologia , Paeonia , Panax , Extratos Vegetais/farmacologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Citocinas/genética , Citocinas/metabolismo , Combinação de Medicamentos , Eritropoetina/biossíntese , Eritropoetina/genética , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Materia Medica/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Transplante de Neoplasias , Paeonia/química , Panax/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Sarcoma 180/tratamento farmacológico , Sarcoma 180/patologia , Fator de Células-Tronco/biossíntese , Fator de Células-Tronco/genética , Trombopoetina/biossíntese , Trombopoetina/genéticaRESUMO
El lupus eritematoso generalizado (LEG) es una enfermedad autoinmune en la que existe un claro desequilibrio en la red que forman las diversas citocinas, con deficiente producción de algunas y exceso de producción de otras, lo que parece repercutir en las diferentes manifestaciones clínicas de la enfermedad. Esta noción, sin embargo, deriva de estudios que se han concentrado en el análisis de una o dos citocinas en particular, y son pocos los que han analizado en un mismo tiempo a todas las posibles citocinas involucradas en la patogénesis del LEG: Por ello decidimos estudiar simultáneamente la transcripción del gen de interleucina IL-1b, IL-2, IL-4, IL-6, IL-10, factor de necrosis tumoral (TNFa), factor de estimulación del crecimiento (TGF-b) e interferón (IFN-g) en células mononucleares de sangre periférica de 17 mujeres con LEG así como en 10 mujeres normales. La transcipción del gen de las diferencias citocinas de estudió mediante la reacción de transcriptasa reversa seguida de la reacción en cadena de la polimerasa y semicuantificada ésta por densitometría. Se encontraron niveles elevados de transcipción de los genes de IL-4, IL-6, IL-10 y TNF-a en todas las pacientes estudiadas mientras que los niveles de transcripción de las citocinas restantes fueron bajos o no detectables. La mayor expresión e transcripción de citocinas con potente efecto sobre la proliferación y diferenciación de linfocitos B sugiere que estas moléculas mantienen el desequilibrio de la red de citocinas favoreciendo la hiperactividad de las células B