RESUMEN
BACKGROUND: Diabetes is a chronic metabolic disease that affects many parts of the body. Considering diabetes as a beta cells' defect and loss, the focus is on finding mechanisms and compounds involved in stimulating the function and regeneration of pancreatic ß-cells. DNA methylation as an epigenetic mechanism plays a pivotal role in the ß-cells' function and development. Considering the regenerative and anti-diabetic effects of Rosa canina extract, this study aimed to assess the methylation levels of Pdx-1, Pax-4, and Ins-1 genes in diabetic rats treated with Rosa Canina extract. METHODS AND RESULTS: Streptozotocin-induced diabetic rats were used to evaluate the frequency of Pdx-1, Pax-4, and Ins-1 gene methylation. Treatment groups were exposed to Rosa canina as spray-dried and decoction extracts. Following blood glucose measurement, pancreatic DNA was extracted and bisulfited. Genes' methylation was measured using MSP-PCR and qRT-PCR techniques. Oral administration of Rosa canina extracts significantly reduced blood sugar levels in diabetic rats compared to the control group. The methylation levels of the Pdx-1, Pax-4, and Ins-1 genes promoter in streptozotocin-induced diabetic rats increased compared to the control rats while, the treatment of diabetic rats with Rosa canina extracts, spray-dried samples especially, led to a decreased methylation in these genes. CONCLUSION: The results of this study showed that Rosa canina extract as a spray-dried sample could be effective in treating diabetes by regulating the methylation of genes including Pdx-1, Pax-4, and Ins-1 involved in the activity and regeneration of pancreatic islet cells.
Asunto(s)
Glucemia , Metilación de ADN , Diabetes Mellitus Experimental , Extractos Vegetales , Rosa , Transactivadores , Animales , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/tratamiento farmacológico , Rosa/química , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Ratas , Extractos Vegetales/farmacología , Masculino , Transactivadores/genética , Transactivadores/metabolismo , Glucemia/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Estreptozocina , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/metabolismo , Insulina/metabolismoRESUMEN
Abstract The present study was aimed to investigate the in vivo effects of Rosa canina extract on doxorubicin-induced testicular toxicity in mice for the first time. Male NMRI mice were randomly divided into six treatment groups (10=per group) as follows: (I) vehicles, (II) doxorubicin alone (3 mg/kg, i.p. on days 7, 14 and 21), (III and IV): Rosa canina extract alone (100 mg/kg and 200 mg/kg per day, i.p. for 28 days), (V and VI) Rosa canina extract plus doxorubicin (each dose given 1 h post Rosa canina). Doxorubicin-treated mice displayed smaller body and testicular weights, decreased serum levels of testosterone, loss in the number of germ cells and Sertoli cells, and reduced sperm count, viability, morphology and motility. Doxorubicin treatment significantly decreased the mean testis diameter, seminiferous tubular diameter and seminiferous epithelial height and increased seminiferous luminal diameter. However, Rosa canina pretreatment could effectively improve all of these abnormalities in doxorubicin- treated mice. The treatment with a higher dose of the extract (200 mg/kg) was more effective compared to doxorubicin and the lower dose of the extract. These findings suggested that the Rosa canina extract has protective effects against doxorubicin-induced reproductive toxicity.
