RESUMEN
The present study has been aimed to explore the different secondary messengers of the inflammatory pathway NF-κB, kinases (JNK, P38MAPK, GSK3ß/ßcatenin), apoptosis pathway (Caspase-3 and AIF), and neuronal survival pathway (BDNF) in order to understand the neuroprotective mechanism of aqueous extract of Tribulus terrestris (AQTT). In primary cortical neurons, the ischemic condition was induced through oxygen-glucose deprivation (OGD). Anti-inflammatory activity of AQTT was evaluated in formalin induced inflammation model and carrageenan-induced paw edema test. The bilateral common carotid artery occlusion model was employed for whole animal studies. Treatment of AQTT (100 mg/kg) significantly reduced the inflammation induced by formalin and carrageenan. The neuroprotective mechanism of AQTT (50 and 100 mg/kg) was assessed by pre- and post-administration. The results indicate down regulation of kinases and NFkB, suggesting possible anti-inflammatory activity of AQTT. Additionally, AQTT down regulated both caspase dependent and independent apoptotic pathways suggesting its possible anti-apoptotic activity. The treatment of AQTT also reduced GSK3ß levels and increased p-Ser9 GSK3ß levels; stabilizing the unphosphorylated form of ß-catenin and its translocation into the nucleus suggesting role of AQTT in neuronal survival and GSK3ß mediated anti-inflammatory property. In comparison to pretreatment, post treatment of AQTT had lesser effects indicating tribulusterine standardized AQTT may have prophylactic effect. This study can be concluded with the thesis that AQTT has neuroprotective effect through alternating neuroinflammation, apoptosis, and promoting neuron survival. Being that it produced better effect with pretreatment, exploring this with thrombolytic drugs will be beneficial. For the first time AQTT has been reported for this indication.
Asunto(s)
Inflamación/metabolismo , Neuronas/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Tribulus/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Glucosa/metabolismo , Masculino , Ratones Endogámicos C57BL , Neuronas/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
The aim of this work was to synthesize selected thiophene-derived aminophosphonic systems and evaluate the phytotoxicity of newly obtained products according to the OECD 208 Guideline. Seven new thiophene-derived N-substituted dimethyl aminomethylphosphonic acid esters 2a-h were synthesized by the addition of an appropriate phosphite to azomethine bond of starting Schiff bases 1a-h, and NMR spectroscopic properties of aminophosphonates were investigated. These eight compounds were analyzed in regard to their phytotoxicity towards two plants, radish (Raphanus sativus) and oat (Avena sativa). On the basis of the obtained results, it was found that tested aminophosphonates 2a-h showed an ecotoxicological impact against selected plants, albeit to various degrees.
Asunto(s)
Tiofenos/química , Tiofenos/farmacología , Tribulus/efectos de los fármacos , Tribulus/crecimiento & desarrollo , Raphanus/efectos de los fármacos , Raphanus/crecimiento & desarrollo , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Tiofenos/síntesis químicaRESUMEN
INTRODUCTION: Herbal preparations have long been used as folk remedies for erectile dysfunction (ED). AIM: This study examined the effects of Tribulus terrestris and Cornus officinalis extracts on relaxation of the smooth muscle of the corpus cavernosum (CC), their mechanisms of action, and the effects of oral administration of a mixture of the herbal extracts on penile erection. METHODS: The relaxation effects and the mechanisms of action of T. terrestris extract, C. officinalis extract, and the mixture of both extracts on the rabbit CC were investigated in an organ bath. To evaluate whether the relaxation response of the CC shown in an organ bath occurs in vivo, intracavernous pressure (ICP) was calculated in rats after oral administration for a month. Additionally, adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic monophosphate (cGMP) in the CC were measured using immunoassay. MAIN OUTCOME MEASURES: Smooth muscle relaxation was expressed as the percent decrease in precontraction induced by phenylephrine. ICP was assessed in rats after the oral administration of a mixture of both extracts for 1 month and changes in cGMP and cAMP concentrations were measured based on the concentration of the mixture of both extracts. RESULTS: T. terrestris extract, C. officinalis extract, and the mixture of both extracts showed concentration-dependent relaxation effects of the CC. In both the endothelium-removed group and N(G)-nitro-L-arginine methyl ester pretreatment group, T. terrestris extract inhibited relaxation. ICP measured after oral administration of the extract mixture for a month was higher than that measured in the control group, and a significant increase in cAMP was observed in the mixture group. CONCLUSIONS: T. terrestris extract and C. officinalis extract exhibited concentration-dependent relaxation in an organ bath. In the in vivo study of the extract mixture, ICP and cAMP was significantly potentiated. Accordingly, the mixture of T. terrestris extract and C. officinalis extract may improve erectile function.