Hypericum perforatum L. (St John's wort) extract Ze 117 inhibits dopamine re-uptake in rat striatal brain slices. An implication for use in smoking cessation treatment?

Classic synthetic antidepressant drugs, as well as St John's wort extract (SJW), directly inhibit the re-uptake of norepinephrine (NE) and/or serotonin (5-HT) into pre-synaptic axons. With chronic treatment they induce adaptive changes in a number of neurotransmitter receptors in synaptic membranes. The immediate effects of SJW Ze 117, an extract low in hyperforin content, on the specific dopamine (DA) uptake were studied in rat striatal brain slices and compared with the effects on NE and 5-HT uptake in rat cortical brain slices. Specific DA uptake was inhibited in a dose dependent manner. In contrast to the findings in synaptosomal preparations published so far, the extract showed different inhibitory potencies for the respective transporters. The potencies for the uptake inhibition of NA, DA and 5-HT were 30, 7 and 1, respectively. The results indicate that the SJW Ze 117 extract interferes in three ways with the individual uptakes of the relevant neurotransmitters that are considered to be causal in the development of depression. This observation, the concomitant and potent inhibition of DA re-uptake by SJW extract, may additionally provide a rationale for the treatment of nicotine or drug addiction with SJW.

Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus.

A large production of leukotrienes (LTs) can be induced in human eosinophils or neutrophils by priming with granulocyte-macrophage colony-stimulating factor and subsequent stimulation with platelet-activating factor (PAF) or the anaphylatoxin C5a. Here, we investigated the effects of a plant extract of petasites hybridus (Ze339) and its isolated active sesquiterpene ester petasin in these two in vitro cell models. Zileuton, a 5-lipoxygenase inhibitor, was used as a positive control. All compounds inhibited both cysteinyl-LT synthesis in eosinophils and LTB(4) synthesis in neutrophils. In contrast, only Ze339 and petasin, but not zileuton, abrogated PAF- and C5a-induced increases in intracellular calcium concentrations. These data suggest that Ze339 and petasin may block, compared to zileuton, earlier signalling events initiated by G protein-coupled receptors in granulocytes, perhaps at the level of or proximal to phospholipase C(beta). Taken together, petasin appears to be one major active compound of petasites hybridus extract, since it demonstrates the same inhibitory activities on calcium fluxes and subsequent LT generation in both eosinophils and neutrophils as Ze339 does.

Antioxidant and thyroid hormone status in selenium-deficient phenylketonuric and hyperphenylalaninemic patients.

BACKGROUND: Subjects consuming protein-restricted diets, such as patients with phenylketonuria (PKU) or milder hyperphenylalaninemias (HPAs) are at risk of selenium deficiency. Selenium is a cofactor of the antioxidant enzyme glutathione peroxidase and of the thyroid hormone converting enzyme thyroxine deiodinase. OBJECTIVE: Our goal was to investigate the effects of low plasma selenium on antioxidant and thyroid hormone status. DESIGN: We assessed plasma selenium, plasma total antioxidant status and the individual components thereof, erythrocyte antioxidant status, and plasma thyroid hormones in 24 PKU and 10 HPA patients and in 42 age-matched control subjects. RESULTS: Selenium was significantly lower in both PKU and HPA patients than in control subjects and the PKU patients had lower values than did the HPA patients. Total antioxidant status was lower in both patient groups than in the control group, whereas alpha-tocopherol, albumin, and uric acid were not significantly different among groups. Plasma selenium correlated well (r = 0.76) with erythrocyte glutathione peroxidase. PKU patients had lower glutathione peroxidase activity than did HPA patients and control subjects and lower glutathione concentrations than did control subjects. Both patient groups had lower superoxide dismutase activity than did control subjects. Free triiodothyronine was higher in both patient groups than in control subjects, whereas free thyroxine was higher in the PKU patients only. Free thyroxine and reverse triiodothyronine were inversely correlated with selenium. CONCLUSION: Supplementation with selenium seems to be advisable for patients consuming diets low in natural protein.

Leguminosae in the diet: the raffinose-stachyose question.

Adhering to a galactose-free diet by strictly avoiding dairy products and known hidden sources of galac-tose does not completely normalize galactose-1-phosphate (gal-1-P) in erythrocytes from patients with galactosemia. Major neurological complications, even in the best treated patients, are threatening a good clinical outcome and dictate a continuous search for leaks in the dietary regimen. Raffinose and stachyose, present in important amounts in various vegetables, contain alpha-1,4 linked galactose which is cleaved only by bacterial alpha-galactosidases, presumably in the lower part of the gut. In order to test the hypothesis whether galactose released from raffinose and stachyose could be a source of absorbed galactose and a cause of elevated gal-1-P six patients with galactosemia (aged 6-24 years), underwent a raffinose- and stachyose-poor dietary regimen for 2 weeks. Before, after, and during the test period, the daily intake of stachyose and raffinose as well of protein, carbohydrate, fat and minerals was calculated from food protocols obtained from the patients. Plasma galactose and erythrocyte gal-1-P were measured at the end of the three test phases. Stachyose and raffinose intake was reduced to 5%-10% during the experimental diet, which was well tolerated, except for constipation in some patients. In five of the six patients gal-1-P in erythrocytes was somewhat lower (statistically not significant) during the test phase than during regular diet while plasma galactose remained unchanged. Galactose released from raffinose and stachyose may be absorbed and contribute to elevated gal-1-P values in erythrocytes of galactosemic patients.

Vesicular transport of sulfatide in the myelinating mouse brain. Functional association with lysosomes?

Sulfatide synthesis and its subcellular distribution kinetics was followed in the myelinating brain of 17-day-old mice. Pulse-labeling-chasing conditions were achieved by an intraperitoneal injection of (35S)sulfate followed 2 h later by a second injection of a high dose of unlabeled sulfate. At 1, 2, 3, 4, and 6 h after the (35S)sulfate injection, the brains were removed, homogenized, and subcellular fractions were obtained by differential and discontinuous sucrose gradient centrifugation (Eichberg, J., Whittaker, V. P., and Dawson, R. M. (1964) Biochem. J. 92, 91-100). The microsomal membranes were further subfractionated (Siegrist, H. P., Burkart, T., Wiesmann, U. N., Herschkowitz, N. N., and Spycher, M. A. (1979) J. Neurochem. 33, 497-504) into light myelin, plasma membranes, Golgi vesicles, endoplasmic reticulum membranes, and heavy vesicles associated with acid hydrolase activities. The [35S]sulfatide-labeling kinetics was measured in all subcellular fractions. The results indicate that sulfatides are synthesized in the Golgi-endoplasmic reticulum complex and transferred in vesicles at least partially associated with lysosomes to the myelin membranes. The association of sulfatides with lysosomes could explain the existence of the previously described labile pool of newly synthesized sulfatides (Burkart, T., Hofmann, K., Siegrist, H. P., Herschkowitz, N. N., and Wiesmann, U. N. (1981) Dev. Biol. 83, 42-48) and also could be a form of vesicular transport to the myelin.