The Ameliorating Effect of Myrrh on Scopolamine-Induced Memory Impairments in Mice.

Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM) on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments.

Ginkgo biloba extract (Egb761) attenuates zinc-induced tau phosphorylation at Ser262 by regulating GSK3ß activity in rat primary cortical neurons.

In the brain, an excessive amount of zinc promotes the deposition of ß-amyloid proteins and the intraneuronal accumulation of neurofibrillary tangles composed of hyperphosphorylated tau proteins. These consequences are key neuropathological traits that reflect Alzheimer's disease. Egb761, a standardized Ginkgo biloba extract, is a powerful antioxidant known to exhibit neuroprotective actions. In this study, we investigated whether Egb761 can counteract the zinc-induced tau phosphorylation in rat primary cortical neurons. To determine the modification of tau phosphorylation by Egb761 treatment, we conducted Western blot analyses, MTT assay, ROS measurements and immunocytochemistry. We found that zinc-induced tau phosphorylation occurred at Ser262 in a time- and dose-dependent manner while other tau sites were not phosphorylated. Tau phosphorylation at Ser262 was increased 30 min after zinc treatment and peaked 3 h after zinc treatment (control: 100 ± 1.2%, 30 min: 253 ± 2.24%, 3 h: 373 ± 1.3%). Interestingly, Egb761 treatment attenuated the zinc-induced tau hyperphosphorylation at Ser262 in a concentration-dependent manner while the antioxidant N-acetylcysteine showed a similar effect. Furthermore, Egb761 prevented the zinc-induced activation of p38 MAPK and GSK3ß, as well as the zinc-induced increase in ROS production and neuronal cell death. Lithium chloride also inhibited the zinc-induced tau phosphorylation but did not affect ROS levels. These results suggest the potential of Egb761 for inhibiting the zinc-induced tau phosphorylation at Ser262 through its anti-oxidative actions involving the regulation of GSK3ß. Therefore, Egb761 may be a candidate for the treatment of tauopathy present in neurological disorders such as Alzheimer's disease.

Uric acid attenuates nitric oxide production by decreasing the interaction between endothelial nitric oxide synthase and calmodulin in human umbilical vein endothelial cells: a mechanism for uric acid-induced cardiovascular disease development.

The elevated level of uric acid in the body is associated with increased risk of cardiovascular diseases, which is mediated by endothelial dysfunction. However, its underlying mechanism is not fully understood, although dysregulation of endothelial nitric oxide (NO) production is likely to be involved. Using human umbilical vascular endothelial cells (HUVEC), we explored the molecular mechanism of uric acid on endothelial NO synthase (eNOS) activity and NO production. Although high dose of uric acid (12mg/dl for 24h treatment) significantly decreased eNOS activity and NO production, it did not alter eNOS expression and phosphorylations at eNOS-Ser(1177), eNOS-Thr(495) and eNOS-Ser(114). Under this condition, we also found no alterations in the dimerization and acetylation of eNOS, compared with the control. Furthermore, uric acid did not change the activity of arginase II, an enzyme degrading l-arginine, a substrate of eNOS, and intracellular level of calcium, a cofactor for eNOS activation. We also found that uric acid did not alter xanthine oxidase activity, suggesting no involvement of xanthine oxidase-derived O2(-) production in the observed inhibitory effects. In vitro and in cell coimmunoprecipitation studies, however, revealed that uric acid significantly decreased the interaction between eNOS and calmodulin (CaM), an eNOS activator, although it did not change the intracellular CaM level. Like in HUVEC, uric acid also decreased eNOS-CaM interaction in bovine aortic EC. Finally, uric acid attenuated ionomycin-induced increase in the interaction between eNOS and CaM. This study suggests firstly that uric acid decreased eNOS activity and NO production through reducing the binding between eNOS and CaM in EC. Our result may provide molecular mechanism by which uric acid induces endothelial dysfunction.