Molecular signalling of a novel curcumin derivative versus Tadalafil in erectile dysfunction

The efficacy of a novel curcumin derivative (NCD) versus tadalafil in erectile signalling was assessed. Ten control male rats and 50 diabetic male rats were used and divided into the following: diabetic (DM), curcumin (CURC), NCD, tadalafil and NCD combined with tadalafil rat groups. Cavernous tissue gene expression of heme oxygenase‐1 (HO‐1), Nrf2, NF‐B and p38, enzyme activities of heme oxygenase (HO) and nitric oxide synthase (NOS), cGMP and intracavernosal pressure (ICP)/mean arterial pressure (MAP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction (ED) was confirmed by the significant decrease in ICP/MAP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO‐1 gene and a significant increase in NF‐?β, p38 genes. Administration of all therapeutic interventions led to a significant increase in ICP/MAP, cGMP levels, a significant increase in HO‐1 and NOS enzymes, a significant increase in HO‐1, and Nrf2 gene expression, and a significant decrease in NF‐?β, p38 gene expression. NCD or its combination with tadalafil showed significant superiority and more prolonged duration of action. In conclusion, a tendency was observed that CURC and NCD have high efficacy and more prolonged duration of action in enhancing erectile function.     

An association between ethanol-evoked enhancement of c-jun gene expression in the nucleus tractus solitarius and the attenuation of baroreflexes

BACKGROUND: An increased expression of Fos, the protein product of the immediate early gene c-fos, in the nucleus tractus solitarius (NTS) is associated with dysfunction in baroreceptor reflex control of heart rate. Our previous studies demonstrated that ethanol attenuates baroreflex sensitivity (BRS) in rats and humans. In this study, we tested the hypothesis that enhanced expression of the immediate early gene c-jun (an index of neuronal activity) in the NTS contributes to the baroreflex dysfunction caused by ethanol. METHODS: Conscious male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were used to measure blood pressure, heart rate, and baroreflex sensitivity (Oxford method). The c-jun messenger RNA (mRNA) expression in NTS was measured by in situ hybridization. RESULTS: Ethanol elicited dose-dependent attenuation in BRS in WKY rats, which was associated with significant increases in c-jun mRNA in the NTS. In contrast, ethanol had no effect on BRS or c-jun mRNA in the NTS of the SHRs; the latter exhibited significantly lower BRS and higher c-jun mRNA in the NTS compared with WKY rats. CONCLUSIONS: An increased basal level of c-jun mRNA in the NTS may contribute to the reduced BRS in the SHR, and ethanol enhancement of neuronal activity of the NTS, expressed as increased c-jun mRNA expression, may contribute to its attenuation of BRS, which highlights the NTS as a neuroanatomical target for ethanol action on baroreflexes.