Neuroprotective Properties of Standardized Extracts of Hypericum perforatum on Rotenone Model of Parkinson's Disease.

Hipericum perforatum is a well-known herbal for its antidepressant property. Recently, it has been shown to have nootropic effects against neurodegenerative disorders. The aim of the present study was to evaluate the protective role of chronic administration of two standardized extract of Hypericum perforatum SHP1 rich in hyperforin (6%) and SHP2 extract poor in hyperforin (0.2%) on the neurodegeneration induced by chronic administration of rotenone in rats. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions. The animals received pretreatments with SHP1 (4 mg/Kg, ip), SHP2 (4 mg/Kg, ip) or quercetin liposomes (25 and 100 mg/kg, ip) 60 min before of rotenone injection (2.5 mg/kg) for 45 days. Pretreatment of the animals with SHP1 and SHP2 efficiently halted deleterious toxic effects of rotenone, revealing normalization of catalepsy in addition to amelioration of neurochemical parameters. Also, SHP1 reduced neuronal damage, diminishing substantia nigra dopaminergic cell death caused by the pesticide, indicating benefit of neuroprotective therapy. In general, the SHP1 was more active than SHP2. In addition, SHP1 inhibited the apoptotic cascade by decreasing Bax levels. The results presented here indicate that mainly hyperforin and quercetin, may be involved in the neuroprotective action of Hypericum standardized extracts. Combination of dietary antioxidants could provide better therapeutic advantage for the management of Parkinson, and possibly other neurodegenerative disorders. Therefore H. perforatum standardized extract enriched in hyperforin, could be a better alternative for depressed elderly patients with degenerative disorders exhibiting elevated oxidative stress status.

Beer consumption reduces cerebral oxidation caused by aluminum toxicity by normalizing gene expression of tumor necrotic factor alpha and several antioxidant enzymes.

Aluminum (Al)-induced neurotoxicity is well known and different salts of aluminum have been reported to accelerate oxidative damage to biomolecules. The present study has examined whether silicon consumed in the form of silicic acid or beer could potentially inhibit aluminum toxicity in the brain. Male mice were administered with Al(NO(3))(3) orally at a dose of 450 mg/kg/day in drinking water for 3 month. Experimental mice were given Al(NO(3))(3) along with 50 mg/L of silicic acid or with 0.5 ml/day of beer. Al brain levels in the Al group were four times higher than those of control mice while silicic acid and beer group values were 40% lower than those of the Al group. We have observed that beer prevented accumulation of lipid damage significantly, which resulted from aluminum intake. Decline in the expression of mRNA of endogenous antioxidant enzymes associated with aluminum administration was also inhibited by beer and silicic acid. The tumor necrosis factor alpha (TNFalpha) RNA expression was normalized in silicic acid and beer groups. Very high and significant correlations were found for the different parameters tested suggesting that moderate consumption of beer, due to its silicon content, effectively protects against the neurotoxic effects of aluminum.

Standardized Hypericum perforatum reduces oxidative stress and increases gene expression of antioxidant enzymes on rotenone-exposed rats.

Since oxidative stress is implicated in the pathophysiology of dementia and depression, this study was designed to investigate the pro-oxidant activity of rotenone, the protective role of standardized extract of Hypericum perforatum (SHP), as well as the mRNA levels of antioxidant enzymes, in brain homogenates of rats following exposure to rotenone and SHP extract. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions to serve as a positive control. The animals received pretreatment with SHP (4 mg/kg) or quercetin liposomes (25 and 100 mg/kg) 60 min before of rotenone injection (2 mg/kg). All treatments were given intraperitoneally in a volume of 0.5 ml/kg body weight, for 45 days. Rotenone treatment increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). The content of reduced glutathione (GSH) was decreased due to chronic rotenone treatment. Rotenone significantly induced the gene expression of CuZnSOD, MnSOD; CAT and GPx in brain. In contrast, SHP extract exerted an antioxidant action which was related with a decreased of MnSOD activity and mRNA levels of some antioxidant enzymes evaluated. Liposomal quercetin treatment resulted in a significant preservation of the activities of antioxidant enzymes and a decreased in the mRNA levels of these antioxidant enzymes. One possible mechanism of action of SHP extract may be related to quercetin in protecting neurons from oxidative damage. Therefore standardized extract of H. perforatum could be a better alternative for depressed elderly patients with degenerative disorder exhibiting elevated oxidative stress status.

Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes.

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.

[Data on the biochemical significance of nickel]. / Algunos datos sobre la significación bioquímica del níquel.

Pharmacokinetics of nickel chloride (63Ni) in blood and cerebral structures in male Wistar Rats is studied. After intravenous administration of 100 microCi 63 Ni, the trace element is distributed after an open bicompartmental model with a high alfa deposition constant, and the point obtained at 20 min. is considered in phase alfa. The kinetics of 63Ni in cerebral structures after the intracerebroventricular administration shows that hypocampus is the structure that most quickly reaches its maximal concentration. Mesencephalon shows slower penetration. Hypothalamus and hypocampus present greater accumulation of the radionucleide as compared with cortex and cerebellum which present a minor one. Insulin secretion of isolated and perfused rat pancreas from animals ingesting nickel in drink water after the stimulus with 16.7 mM glucose, is greater (53,35 ng immunoreactive insulin/min) than in control animals (30,42 ng immunoreactive insulin/min). In in vivo experiments, after a stimulus with 0,5 g glucose/Kg rat, for the 200 micrograms Ni/ml drinking water and control groups, there was an insulin secretion of 14 microunits insulin/ml and 2 microunits insulin/ml respectively. The normal plasmatic levels of insulin do not show any difference in both, nickel drinking water and controls. Nickel ion in drinking water induces the accumulation of calcium and zinc by the rat pancreas from 2.7 to 4 micrograms/mg protein and from 0.8 to 1.3 micrograms mg protein respectively. Both ions are essential cations for pancreatic physiological function and the synthesis of insulin.