RESUMEN
Our previous studies have demonstrated that phytoestrogen α-zearalanol (α-ZAL) possesses potential benefits in alleviating cell apoptotic death just like oestrogen. However, the underlying mechanism is not fully understood. This study was designed to test the hypothesis that the neuroprotective effect of α-ZAL is mediated by oestrogen receptor (ER) as α-ZAL owns the benzene ring structure may interact with ER. The present results showed a significant increase in apoptosis in differentiated PC12 cells after a 24-hr exposure to amyloid ß-peptide fragment 25-35 (Aß25-35 ), accompanied by decreasing of bcl-2 expression and increasing bax expression, whereas a pre-treatment with α-ZAL ameliorated these changes induced by Aß25-35 . In addition, the α-ZAL-mediated cytoprotection was abrogated by ERα antagonist but not by ERß antagonist. In summary, these data suggest that α-ZAL intervenes against Aß-induced apoptosis via intersecting bcl-2-bax apoptotic pathway in an ERα-sensitive manner.
Asunto(s)
Receptor alfa de Estrógeno/metabolismo , Fármacos Neuroprotectores/farmacología , Fitoestrógenos/farmacología , Zeranol/farmacología , Péptidos beta-Amiloides/farmacología , Animales , Apoptosis/efectos de los fármacos , Diferenciación Celular , Células PC12 , Fragmentos de Péptidos/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ratas , Proteína X Asociada a bcl-2/genéticaRESUMEN
The present study was designed to elucidate the potential mechanism underlying that berberine suppressed ischemic arrhythmias in a rat model of diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending (LAD) coronary artery. Berberine was orally administered for 7 days before ischemic injury in diabetic rats. Whole-cell patch-clamp was performed to measure the transient outward K⺠current (I(to)) and L-type Ca²âº current (I(Ca)). Results showed that oral administration of berberine (100 mg/kg) attenuated ischemia-induced arrhythmias in diabetic rats. Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats, and also restored the diminished I(to) and I(Ca) current densities in the same animal model rats. In conclusion, the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospective therapeutic agent in clinical management of cardiac disease secondary to diabetes.