RESUMEN
AIM OF THE STUDY: Chinese herbal medicine has been used for the treatments of various diseases for years. However, it is often difficult to analyze their biological activities and molecule mechanisms because of their complex nature. In this study, we applied DNA microarray to analyze the biological events induced by herbal formulae, predict the therapeutic potentials of formulae, and evaluate the safety of formulae. MATERIALS AND METHODS: Mice were administrated orally with 15 formulae for 7 consecutive days, and the gene expression profiles in liver or kidney were further analyzed by transcriptomic tools. RESULTS: Our data showed that most formulae altered the metabolic pathways, such as glutathione metabolism and oxidative phosphorylation, and regulatory pathways, such as antigen processing and presentation and insulin-like growth factor signaling pathway. By comparing the gene expression signatures of formulae with those of disease states or drugs, we found that mice responsive to formula treatments might be related to disease states, especially metabolic and cardiovascular diseases, and drugs, which exhibit anti-cancer, anti-inflammatory, and anti-oxidative effects. Moreover, most formulae altered the expression levels of cytochrome p450, glutathione S-transferase, and UDP glycosyltransferase genes, suggesting that caution should be paid to possible drug interaction of these formulae. Furthermore, the similarities of gene expression profiles between formulae and toxic chemicals were low in kidney, suggesting that these formulae might not induce nephrotoxicities in mice. CONCLUSIONS: This report applied transcriptomic tools as a novel platform of translational medicine for Chinese herbal medicine. This platform will not only for understanding the therapeutic mechanisms involving herbal formulae and gene interactions, but also for the new theories in drug discovery.
Asunto(s)
Bases de Datos Factuales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/toxicidad , Animales , Evaluación Preclínica de Medicamentos , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Transducción de Señal/efectos de los fármacos , Transcripción GenéticaRESUMEN
Pulmonary inflammation is a characteristic of many lung diseases. Increased levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines, such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and IL-8, have been correlated with lung inflammation. In this study, we used lipopolysaccharide (LPS) to induce iNOS, COX-2, and cytokines (TNF-alpha, IL-1beta, and IL-8) productions in human lung epithelial cells (A-549). Leaf of Eriobotrya japonica (Pi-Pa-Ye, PPY), a traditional Chinese medicine for the treatment of pulmonary inflammatory diseases, was capable of suppressing LPS-induced cytokine productions in a dose-dependent manner. Moreover, the suppression of PPY on the cytokine productions resulted from the inhibition of inhibitory kappaB-alpha phosphorylation and nuclear factor-kappaB (NF-kappaB) activation. Analysis of the anti-inflammatory effects of ursolic acid and oleanolic acid, the triterpene compounds present in PPY, showed that ursolic acid significantly inhibited LPS-induced IL-8 production, NF-kappaB activation, and iNOS mRNA expression, whereas oleanolic acid did not have these effects. In conclusion, our findings suggested the potential mechanisms of PPY and its active component, ursolic acid, in the treatment of pulmonary inflammation.
Asunto(s)
Citocinas/inmunología , Medicamentos Herbarios Chinos/farmacología , Eriobotrya/química , Pulmón/inmunología , FN-kappa B/inmunología , Transducción de Señal/efectos de los fármacos , Triterpenos/farmacología , Línea Celular , Medicamentos Herbarios Chinos/química , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , Células Epiteliales/inmunología , Expresión Génica/efectos de los fármacos , Humanos , Lipopolisacáridos/inmunología , Pulmón/efectos de los fármacos , Pulmón/enzimología , Hojas de la Planta/químicaRESUMEN
Traditional Chinese medicine (TCM) has been used for thousands of years. Most Chinese herbal formulae consist of several herbal components and have been used to treat various diseases. However, the mechanisms of most formulae and the relationship between formulae and their components remain to be elucidated. Here we analyzed the putative mechanism of San-Huang-Xie-Xin-Tang (SHXXT) and defined the relationship between SHXXT and its herbal components by microarray technique. HepG2 cells were treated with SHXXT or its components and the gene expression profiles were analyzed by DNA microarray. Gene set enrichment analysis indicated that SHXXT and its components displayed a unique anti-proliferation pattern via p53 signaling, p53 activated, and DNA damage signaling pathways in HepG2 cells. Network analysis showed that most genes were regulated by one molecule, p53. In addition, hierarchical clustering analysis showed that Rhizoma Coptis shared a similar gene expression profile with SHXXT. These findings may explain why Rhizoma Coptis is the principle herb that exerts the major effect in the herbal formula, SHXXT. Moreover, this is the first report to reveal the relationship between formulae and their herbal components in TCM by microarray and bioinformatics tools.
Asunto(s)
Carcinoma Hepatocelular/genética , Medicamentos Herbarios Chinos/farmacología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Análisis por Conglomerados , Daño del ADN/efectos de los fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Pulmonary inflammation is a characteristic of many lung diseases. Increased levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), have been correlated with lung inflammation. In this study, we demonstrated that various inflammatory agents, including lipopolysaccharide, 12-o-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid and ceramide, were able to induce IL-1beta and TNF-alpha productions in human lung epithelial cells (A-549), fibroblasts (HFL1), and lymphoma cells (U-937). Berberine, the protoberberine alkaloid widely distributed in the plant kingdom, was capable of suppressing inflammatory agents-induced cytokine production in lung cells. Inhibition of cytokine production by berberine was dose-dependent and cell type-independent. Moreover, the suppression of berberine on the cytokine production resulted from the inhibition of inhibitory kappaB-alpha phosphorylation and degradation. In conclusion, our findings suggested the potential role of berberine in the treatment of pulmonary inflammation.
Asunto(s)
Antiinflamatorios/farmacología , Berberina/farmacología , Proteínas I-kappa B/metabolismo , Inflamación/prevención & control , Interleucina-1beta/metabolismo , Pulmón/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Alcaloides/toxicidad , Antiinflamatorios/toxicidad , Benzofenantridinas/toxicidad , Berberina/toxicidad , Supervivencia Celular/efectos de los fármacos , Ceramidas/farmacología , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrógeno/farmacología , Inflamación/metabolismo , Inflamación/patología , Isoquinolinas/toxicidad , Lipopolisacáridos/farmacología , Pulmón/metabolismo , Pulmón/patología , Inhibidor NF-kappaB alfa , Ácido Ocadaico/farmacología , Fosforilación , Acetato de Tetradecanoilforbol/farmacología , Células U937RESUMEN
In traditional Chinese medicine (TCM), the imbalance of yin and yang is one of the basic pathogeneses of a disease. Preponderance of yang leads to "heat" manifestations including thirst, dryness of the throat, dark scanty urine and constipation. Treatment of asthma in TCM is based on the differentiation of "heat" Zheng according to the manifestations. Some of the patients with allergic asthma also present typical "heat" manifestations. To investigate the essence of "heat" manifestation in asthma, we measured the serum level of eosinophil cationic protein (ECP) in asthmatic patients. ECP usually represents the activation of eosinophils which are the main effectors in late allergic reactions. Our results demonstrated that asthmatic patients with "heat" manifestations had higher serum ECP levels, compared to those without "heat" manifestations (34.3 +/- 4 microg/l versus 15.3 +/- 3 microg/l). However, total immunoglobulin B (IgE), and the eosinophil count in peripheral blood did not show any difference between the "heat" and "non-heat" groups. Therefore, we conclude that ECP in asthmatic patients plays an important role in the development of "heat" manifestations as diagnosed by TCM.