The regional distributions of iron, copper, zinc, magnesium, and calcium in parkinsonian brains were compared with those of matched controls. In mild Parkinson's disease (PD), there were no significant differences in the content of total iron between the two groups, whereas there was a significant increase in total iron and iron (III) in substantia nigra of severely affected patients. Although marked regional distributions of iron, magnesium, and calcium were present, there were no changes in magnesium, calcium, and copper in various brain areas of PD. The most notable finding was a shift in the iron (II)/iron (III) ratio in favor of iron (III) in substantia nigra and a significant increase in the iron (III)-binding, protein, ferritin. A significantly lower glutathione content was present in pooled samples of putamen, globus pallidus, substantia nigra, nucleus basalis of Meynert, amygdaloid nucleus, and frontal cortex of PD brains with severe damage to substantia nigra, whereas no significant changes were observed in clinicopathologically mild forms of PD. In all these regions, except the amygdaloid nucleus, ascorbic acid was not decreased. Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron (III) suggest that these changes might contribute to pathophysiological processes underlying PD.
Abstract. Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as a traditional medicine in China, Korea, and Japan for thousands of years and is now a popular and worldwide used natural medicine. The active ingredients of ginseng are ginsenosides which are also called ginseng saponins. Recently, there is increasing evidence in the literature on the pharmacological and physiological actions of ginseng. However, ginseng has been used primarily as a tonic to invigorate week bodies and help the restoration of homeostasis. Current in vivo and in vitro studies have shown its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency, and hepatotoxicity. Moreover, recent research has suggested that some of ginseng's active ingredients also exert beneficial effects on aging, central nervous system (CNS) disorders, and neurodegenerative diseases. In general, antioxidant, anti-inflammatory, anti-apoptotic, and immune-stimulatory activities are mostly underlying the possible ginseng-mediated protective mechanisms. Next to animal studies, data from neural cell cultures contribute to the understanding of these mechanisms that involve decreasing nitric oxide (NO), scavenging of free radicals, and counteracting excitotoxicity. In this review, we focus on recently reported medicinal effects of ginseng and summarize the current knowledge of its effects on CNS disorders and neurodegenerative diseases.
Dedicated to Prof. Dr S. Ebel on his 70th birthday1 The functional characterization of hispidulin (4 0 ,5,7-trihydroxy-6-methoxyflavone), a potent benzodiazepine (BZD) receptor ligand, was initiated to determine its potential as a modulator of central nervous system activity. 2 After chemical synthesis, hispidulin was investigated at recombinant GABA A /BZD receptors expressed by Xenopus laevis oocytes. Concentrations of 50 nM and higher stimulated the GABAinduced chloride currents at tested receptor subtypes (a 1À3,5,6 b 2 g 2 S) indicating positive allosteric properties. Maximal stimulation at a 1 b 2 g 2 S was observed with 10 mM hispidulin. In contrast to diazepam, hispidulin modulated the a 6 b 2 g 2 S-GABA A receptor subtype.3 When fed to seizure-prone Mongolian gerbils (Meriones unguiculatus) in a model of epilepsy, hispidulin (10 mg kg À1 body weight (BW) per day) and diazepam (2 mg kg À1 BW per day) markedly reduced the number of animals suffering from seizures after 7 days of treatment (30 and 25% of animals in the respective treatment groups, vs 80% in the vehicle group). 4 Permeability across the blood-brain barrier for the chemically synthesized, 14 C-labelled hispidulin was confirmed by a rat in situ perfusion model. With an uptake rate (K in ) of 1.14 ml min À1 g À1 , measurements approached the values obtained with highly penetrating compounds such as diazepam. 5 Experiments with Caco-2 cells predict that orally administered hispidulin enters circulation in its intact form. At a concentration of 30 mM, the flavone crossed the monolayer without degradation as verified by the absence of glucuronidated metabolites.
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