RESUMEN
Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L. that elicits neuroprotective effects in vivo and in vitro. Tyrosol galactoside (Tyr), an analog of Sal, was recently synthesized in our laboratory. The purpose of the current study was to investigate and compare the neuroprotective effects of Sal and Tyr against focal cerebral ischemia in vivo and H(2)O(2)-induced neurotoxicity in vitro. Sal and Tyr significantly prevented a cerebral ischemic injury induced by a 2 h middle cerebral artery occlusion and a 24 h reperfusion in rats in vivo. Furthermore, the oxidative insult was markedly attenuated by treatments of Sal and Tyr in the cultured rat cortical neurons after a 30 min exposure to 50 µM of H(2)O(2). Western blot analysis revealed that Sal and Tyr decreased the expression of Bax and restored the balance of pro- and anti-apoptotic proteins. The neuroprotective effects of these two analogues show that Tyr has a better antioxidative action compared with Sal both in vivo and in vitro, and suggest that the antioxidant activity of Sal and Tyr may be partly due to their different substituents in their glycosyl groups. This gives a new insight into the development of therapeutic natural antioxidants against oxidative stress.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Galactósidos/uso terapéutico , Glucósidos/uso terapéutico , Peróxido de Hidrógeno/antagonistas & inhibidores , Fármacos Neuroprotectores/uso terapéutico , Fenoles/uso terapéutico , Alcohol Feniletílico/análogos & derivados , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Isquemia Encefálica/patología , Supervivencia Celular/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Esquema de Medicación , Galactósidos/administración & dosificación , Galactósidos/farmacología , Glucósidos/administración & dosificación , Glucósidos/farmacología , Peróxido de Hidrógeno/toxicidad , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Masculino , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Oxidantes/antagonistas & inhibidores , Oxidantes/toxicidad , Fenoles/administración & dosificación , Fenoles/farmacología , Alcohol Feniletílico/administración & dosificación , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/uso terapéutico , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
The present study examined the protective effect of hyperbaric oxygen preconditioning (HBO-PC) and the role of thioredoxin reductase (TrxR) in a post-traumatic stress disorder (PTSD)-induced rat model by using single prolonged stress (SPS). Rats were randomly divided into Sham, HBO, SPS and HBO+SPS groups. HBO-PC was conducted by exposing rats to 100% oxygen at 2.5atm absolute for 1h each day for 5 consecutive days. SPS was performed 24h after the last HBO-PC conditioning event. At 1h, 6h, 12h, 24h and 72h after SPS, TrxR mRNA expression was analyzed in the hippocampus; Nissl and TUNEL staining were performed at 72h after SPS. The results indicated that HBO-PC was able to significantly preserve viable neurons in the CA1 subfield of hippocampus following SPS exposure, as evidenced by reduced amounts of CA1 neuronal apoptosis. Furthermore, HBO-PC upregulate the expression of TrxR-1 and TrxR-2 mRNA in the hippocampus at 6h and 12h after SPS exposure and ameliorated anxiety-like behavior and cognitive impairments normally induced by SPS. Taken together, these findings suggest that HBO-PC is beneficial for the improvement of anxiety-like behavior and cognitive impairments induced by SPS exposure, and this effect might be associated with inhibition of neuronal apoptosis via upregulation of TrxR in stressed rats.