RESUMO
The aim of the present study was to assess the effectiveness of Rhizoma Dioscoreae extract (RDE) on preventing rat alveolar bone loss induced by ovariectomy (OVX), and to determine the role of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in this effect. Female Wistar rats were subjected to OVX or sham surgery. The rats that had undergone OVX were treated with RDE (RDE group), vehicle (OVX group) or 17ß-estradiol subcutaneous injection (E2 group). Subsequently, bone metabolic activity was assessed by analyzing 3-D alveolar bone construction, bone mineral density, as well as the plasma biomarkers of bone turnover. The gene expression of alveolar bone in the OVX and RDE groups was evaluated by IL-6/STAT3 signaling pathway polymerase chain reaction (PCR) arrays, and differentially expressed genes were determined through reverse transcription-quantitative PCR. The inhibitory effect of RDE on alveolar bone loss in the OVX group was demonstrated in the study. In comparison with the OVX group, the RDE group exhibited 19 downregulated genes and 1 upregulated gene associated with the IL-6/STAT3 signaling pathway in alveolar bone. Thus, RDE was shown to relieve OVX-induced alveolar bone loss in rats, an effect which was likely associated with decreased abnormal bone remodeling via regulation of the IL-6/STAT3 signaling pathway.
Assuntos
Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Araceae/química , Interleucina-6/metabolismo , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Perda do Osso Alveolar/diagnóstico , Perda do Osso Alveolar/tratamento farmacológico , Animais , Biomarcadores , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia/efeitos adversos , Extratos Vegetais/química , Ratos , Transcriptoma , Microtomografia por Raio-XRESUMO
Rhizoma Dioscoreae extract (RDE) exhibits a protective effect on alveolar bone loss in ovariectomized (OVX) rats. The aim of this study was to predict the pathways or targets that are regulated by RDE, by reassessing our previously reported data and conducting a proteinprotein interaction (PPI) network analysis. In total, 383 differentially expressed genes (≥3fold) between alveolar bone samples from the RDE and OVX group rats were identified, and a PPI network was constructed based on these genes. Furthermore, four molecular clusters (AD) in the PPI network with the smallest Pvalues were detected by molecular complex detection (MCODE) algorithm. Using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA) tools, two molecular clusters (A and B) were enriched for biological process in Gene Ontology (GO). Only cluster A was associated with biological pathways in the IPA database. GO and pathway analysis results showed that cluster A, associated with cell cycle regulation, was the most important molecular cluster in the PPI network. In addition, cyclindependent kinase 1 (CDK1) may be a key molecule achieving the cellcycleregulatory function of cluster A. From the PPI network analysis, it was predicted that delayed cell cycle progression in excessive alveolar bone remodeling via downregulation of CDK1 may be another mechanism underling the antiosteopenic effect of RDE on alveolar bone.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/metabolismo , Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Pinellia/química , Extratos Vegetais/farmacologia , Perda do Osso Alveolar/patologia , Animais , Feminino , Extratos Vegetais/química , RatosRESUMO
This study is to evaluate the effects of Shenmai injection on the temporal alterations of action potential (AP), early afterdepolarization (EAD) and delayed afterdepolarization (DAD) in papillary muscles. The action potentials were recorded by a glass electrode. APD at 90% repolarization (APD9 ) was measured, and spontaneous EAD and DAD were observed. The results show APD90 was significantly prolonged in model group compared with sham-operated group, whereas it was remained unchanged in Shenmai injec- tion treatment group and amiodarone group. The spontaneous EADs and DADs were frequently visible in model group. In conclusion, EAD, DAD and trigger activities increase gradually during pathological progression of rat cardiac hypertrophy, and Shenmai injection could improve the action potential change in rat cardiac hypertrophy.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Cardiomegalia/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Injeções , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To clarify the protective roles of compatibility of geniposide and ginsenoside (Rg1) in regulating ischemia injured microglia homeostasis by comparing the difference in regulatory roles of geniposide, Rg1, or ginsenoside + Rg1 in balancing secretion of oxygen glucose deprivation induced microglia inflammatory cytokines. METHODS: The mimic ischemia injured microglia model was induced by oxygen-glucose deprivation (OGD). Then geniposide, Rg1, or ginsenoside + Rg1 (Tongluo Jiunao Injection, TJI) was respectively added. The NO content was determined by Griess Reagent. The cyto activity was detected using cell count kit. Contents of TNF-alpha and TGF-beta and their expression levels were detected by ELISA and Western blot. RESULTS: Geniposide + Rg1 could significantly inhibit the release of NO, elevate the TGF-beta level, and decrease the content of TNF-alpha without influencing the cell survival. The two active ingredients played different therapeutic roles. The compatible use was obviously superior to use any one of the two active ingredients alone. CONCLUSIONS: Geniposide, Rg1, or Ginsenoside + Rg1 had regulating roles in balancing ischemia injured microglia homeostasis. Its mechanisms might be related to up-regulating the TGF-beta expression and down-regulating TNF-alpha expression.
Assuntos
Ginsenosídeos/farmacologia , Hipóxia/metabolismo , Iridoides/farmacologia , Microglia/efeitos dos fármacos , Animais , Camundongos , Microglia/metabolismo , Óxido Nítrico/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Ecliptae herba (EH) has long been used in China to strengthen bones. Accumulating evidence indicates that EH may have antiosteoporotic effects. The aim of this study was to evaluate the effects of aqueous EH extract (EHE) on rats that had osteoporosis-like features induced by ovariectomy, using aqueous Fructus Ligustri Lucidi extract as positive control agent. METHODS: Three-month-old female rats that underwent ovariectomy were treated with EHE (1.4 g/kg per day). After 12 weeks, bone mineral density and bone histomorphometric indices of tibiae were measured. Protein and messenger RNA expressions of osteoprotegerin and receptor activator of nuclear factor κ-B ligand (RANKL) in tibiae were evaluated by immunohistochemistry and in situ hybridization. In addition, serum concentrations of osteocalcin, interleukin-1ß, interleukin-6 (IL-6), calcitonin (CT), and parathyroid hormone were determined by enzyme-linked immunosorbent assay. RESULTS: EHE treatment prevented body weight gain and loss of uterine wet weight in ovariectomized rats. It remarkably increased bone mass in ovariectomized rats compared with ovariectomized controls. EHE treatment significantly down-regulated RANKL expression in tibiae from ovariectomized rats compared with controls; however, it had no significant effect on osteoprotegerin expression. In addition, EHE treatment significantly reduced serum IL-6 levels and remarkably increased CT levels but had no effect on parathyroid hormone. CONCLUSIONS: EHE increases bone mass in ovariectomized rats by inhibiting bone loss: down-regulated RANKL expression in tibiae and IL-6 level in serum, and up-regulated CT level in serum. This suggests that EHE may be developed as an alternative therapeutic agent for osteoporosis induced by postmenopause.