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Current strategies for the discovery of k(+) channel modulators.

Curr Top Med Chem. 2009; 9(4): 348-61Ye D, Wang J, Yu K, Zhou Y, Jiang H, Chen K, Liu HPotassium ion (K(+)) channels consist of a ubiquitous family of membrane proteins that play critical roles in a wide variety of physiological processes, such as the regulation of neuronal excitability, muscle contraction, cell proliferation, and insulin secretion. Due to their pivotal functions in biological systems, K(+) channels have long been attractive targets for the rational drug design on the basis of their structures and interaction mechanisms. Various small-molecular compounds and toxins have been discovered to act as K(+) channel modulators. In the present review, we will first briefly discuss current knowledge of the structures and functions of K(+) channels, and then review the recent strategies for the discovery of K(+) channel modulators, focusing especially on the virtual screening approaches and chemical synthesis technologies.

The Anti-amnesic Effects of Luteolin against Amyloid ss25-35 Peptide-induced Toxicity in Mice Involve the Protection of Neurovascular Unit.

Neuroscience. 2009 May 11; Rui L, Mei G, Guifen Q, Tiantai Z, Xi L, Jian Y, Guanhua DLuteolin is an important member of the flavonoid family. It exhibits strongly anti-inflammatory, anti-oxidant and phytoestrogen-like activities. In the present study, we examined the anti-amnesic and protective effects of luteolin against Ass(25-35) -induced toxicity in mice. Mice were given an intracerebroventricular injection of aggregated Ass(25-35) peptide. The learning and memory impairments, ultrastructural changes of cerebral cortex, cerebrovascular dysfunction and neuronal changes were detected after oral administration of luteolin continuously for 8 days. Our results demonstrate that oral administration of luteolin for 8 days for those Ass(25-35) -induced amnesic mice conferred robust neurovascular protection in Ass(25-35) -induced amnesia, involving the improvement of the spatial learning and memory capabilities, the modulation of microvascular function, the increase of regional cerebral blood flow values, the clearance of ROS, the improvement of cholinergic neuronal system, and the raise of BNDF level and its receptor TrkB expression in cerebral cortex.

Effect Gardenia Extracts-T9 On Viral Replication

LRT-PCR was used to detect expression level of VP16 mRNA and IFN-gamma mRNA in Herpes simplex virus type-1 infected mice brains at 4th day, 7th day, 10th day, 14th day, 21st day post infection and investigate the effects of the Gardenia extracts-T9 on viral replication and host immunity.

The results showed that expression of VP16 mRNA in Gardenia extracts-T9 high dose and low dose group were both lower than that in virus control group at same time point. Relative VP16 mRNA expression in low dose group decreased at 21st day and relative VP16 mRNA expression in high dose group decreased continuously.

Relative expression of IFN-gamma mRNA in high dose and low dose groups were both higher than that in virus control group at all time point except the 4th day. IFN-gamma mRNA in low dose group increased from the 4th day till the 14th day, and after the 14th day, the expression decreased slightly.

Relative IFN-gamma mRNA in high dose group maintained increasing from 4th day till 21st day. Base on these results, we conclude that Gardenia extracts-T9 might exert the inhibition effect of viral replication by upregulating expression of IFN-gamma mRNA.

"Effect of the gardenia extracts-T9 on viral replication and IFN-gamma mRNA in Herpes simplex virus type-1 infected mice brains"
Bing Du Xue Bao. 2009 Jan; 25(1): 41-6Shi YJ, Huang Y, Jiang J, Guo SS, Su D, Zhao Y, Gao YJ, Cui X

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