Purification, structural elucidation, antioxidant capacity and neuroprotective potential of the main polyphenolic compounds contained in Achyrocline satureioides (Lam) D.C. (Compositae).

Achyrocline satureioides (Lam) D.C (Compositae) is a native medicinal plant of South America traditionally utilized for its anti-inflammatory, sedative and anti-atherosclerotic properties among others. Neuroprotective effects have been reported in vivo and could be associated to its elevated content of flavonoid aglycones.

Nicotine-Induced Neuroprotection in Rotenone In Vivo and In Vitro Models of Parkinson's Disease: Evidences for the Involvement of the Labile Iron Pool Level as the Underlying Mechanism.

Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Clinical and experimental evidence suggest that the activation of the nicotinic acetylcholine receptor (nAChR) could be protective for PD. In this study, we investigated the neuroprotective capacity of nicotine in a rat PD model.

Intravenous nanosomes of quercetin improve brain function and hemodynamic instability after severe hypoxia in newborn piglets.

Perinatal asphyxia is a major cause of death and neurological morbidity in newborns and oxidative stress is one of the critical mechanisms leading to permanent brain lesions in this pathology. In this context we have chosen quercetin, a natural antioxidant, known also by its brain protective effects to study its potential as a therapy for brain pathology provoked by severe hypoxia in the brain. To overcame the difficulties of quercetin to access the brain, we have developed lecithin/cholesterol/cyclodextrin nanosomes as a safe and protective vehicle.

Quercetin in brain diseases: Potential and limits.

Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection.

Antioxidant activity, cellular bioavailability, and iron and calcium management of neuroprotective and nonneuroprotective flavones.

Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca(2+) levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm.

Neuroprotective actions of flavones and flavonols: mechanisms and relationship to flavonoid structural features.

Epidemiological studies have shown positive preventive action of flavonoids on cardiovascular and neurodegenerative events. Among the six groups in which flavonoids are classified, the flavones and flavonols, based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) are the most commonly encountered within the families and genera of the higher plants. Numerous studies support a neuroprotective activity of flavones such as luteolin and flavonols such as kaempherol and quercetin in experimental focal ischemia and models of neurodegeneration.

Life or death: neuroprotective and anticancer effects of quercetin.

Ethnopharmacological Relevance: Quercetin is a ubiquitous flavonoid that is present in numerous plants that are utilized in many different cultures for their nervous system and anticancer effects. To better understand the neuroprotective and antiproliferative activities of quercetin, we present a comprehensive review of the divergent actions that contribute to the ethnopharmacological profile of these plants.

Results: The pharmacological activities of quercetin that modulate antioxidation/oxidation/kinase-signaling pathways might be differentially elicited in neurons compared with malignant cells, ultimately promoting cell survival or death in a cell type- and metabolism-specific manner.

After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult.

In this work we describe the protective effects of quercetin against H(2)O(2) in 24-h-pretreated neuronal cultures. We explored quercetin availability and subcellular fate through the use of HPLC-Diode Array Detection (DAD), epifluorescence, and confocal microscopy. We focused on quercetin modulation of thiol-redox systems by evaluating changes in mitochondrial thioredoxin Trx2, the levels of total glutathione (GSH), and the expression of the gamma-glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme of GSH synthesis, by the use of Western blot, HPLC, and real-time PCR techniques, respectively.

In silico characterization of cytisinoids docked into an acetylcholine binding protein.

Homology models of nicotinic acetylcholine receptors (nAChRs) suggest that subtype specificity is due to non-conserved residues in the complementary subunit of the ligand-binding pocket. Cytisine and its derivatives generally show a strong preference for heteromeric alpha4beta2* nAChRs over the homomeric alpha7 subtype, and the structural modifications studied do not cause large changes in their nAChR subtype selectivity. In the present work we docked cytisine, N-methylcytisine, and several pyridone ring-substituted cytisinoids into the crystallographic structure of the Lymnaea stagnalis acetylcholine binding protein (AChBP) co-crystallized with nicotine (1UW6).

Increase in locomotor activity after acute administration of the nicotinic receptor agonist 3-bromocytisine in rats.

Nicotinic acetylcholine receptors influence striatal dopaminergic activity and its outcome on motor behavior. For these reasons, nicotinic receptors have been considered as therapeutically relevant targets for Parkinson's disease, in which a dramatic loss of dopamine affects motor functions. The aim of the present work was to compare the effects on locomotor activity induced by the nicotinic agonist cytisine and two brominated derivatives, 5- and 3-bromocytisine (5-BrCy and 3-BrCy) using nicotine for comparison.

Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study.

Quercetin shows structural features that have been related to the antioxidant potency of flavonoids and also shows neuroprotection in different models of oxidative death. Because only a few studies have focused on the flavonoid structural requirements for neuroprotection, this work evaluated the protective capacity of 13 flavones structurally related to quercetin, isolated from Kenyan plants, to rescue primary cerebellar granule neurons from death induced by a treatment with 24 h of hydrogen peroxide (150 microM). Each flavone (0-100 microM) was applied 24 h prior to the oxidative insult, and neuronal viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: implications for Parkinson's Disease.

Nicotinic acetylcholine receptor agonists are considered potential pharmacological agents for Parkinson's disease treatment, due to their ability to improve experimental Parkinson symptomatology, reduce 3,4-dihydroxy-L-phenylalanine-induced dyskinesias and stop the neurodegenerative process at an experimental level. In the present work, the ability of the nicotinic agonist cytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to induce striatal dopamine release was characterized in vivo by microdialysis. Cytisine, 5-bromocytisine and nicotine were much more efficacious than 3-bromocytisine in eliciting dopamine release in response to their local application through the microdialysis probe.

Reduction of ischemic brain damage and increase of glutathione by a liposomal preparation of quercetin in permanent focal ischemia in rats.

Oxidative stress is implicated in the pathogenesis of cerebral ischemia injury, and the flavonoids have shown to be neuroprotective in experimental models of cerebral ischemia. Previously, we have shown that an aqueous preparation of quercetin did not reach the brain while a liposomal preparation produced measurable cerebral amounts of quercetin that reduced significantly the cerebral damage provoked by permanent middle cerebral artery occlusion (pMCAo) of rats. In this context, the protective effects of liposomal quercetin (LQ) were investigated in the same model after 1 and 4 hours of arterial occlusion.

Immunomodulatory properties of Achyrocline satureioides (Lam.) D.C. infusion: a study on human leukocytes.

Aim Of The Study: Achyrocline satureioides (Lam.) D.C.

Nicotine induces tyrosine hydroxylase plasticity in the neurodegenerating striatum.

It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus striatum (CS) after 6-hydroxydopamine injection in the substantia nigra. To study the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.

C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists.

Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory roles in the brain, making them attractive therapeutic targets. Natural products provide key leads in the quest for nicotinic receptor subtype-selective compounds. Cytisine, found in Leguminosae spp.

From ligand design to therapeutic efficacy: the challenge for nicotinic receptor research.

S-Nicotine, the principal psychoactive constituent of Nicotiana tabacum, underpins addiction to tobacco smoking. Although tobacco consumption is a leading cause of death worldwide, nicotine itself is also proposed to have potential therapeutic benefits for a diverse range of conditions. Nicotine interacts with its cognate receptors in the central nervous system to exert a predominantly modulatory influence, making neuronal nicotinic receptors attractive therapeutic targets.

Photoprotection by topical application of Achyrocline satureioides ('Marcela').

It has been demonstrated that the use of topical antioxidants can contribute to controling the free radicals excess produced by ultraviolet (UV) irradiation of the skin, being beneficial for processes such as photo aging and eventually cancer. Some plant extracts, particularly because of their polyphenolic constituents, can be beneficial for skin photo damage. Plant extracts of Achyrocline satureioides (AS) and Epilobium parviflorum (EP), potent antioxidant medicinal plants, were mixed with a cosmetic base and applied to the back skin of rabbits.

Some aspects of the in vivo neuroprotective capacity of flavonoids: bioavailability and structure-activity relationship.

On the basis of previous work showing that flavonoids structurally related to quercetin are neuroprotective for cells in culture, this work was directed towards determining if several flavonoids (quercetin, fisetin and catechin) could acutely and by an intraperitoneal (IP) route reach significant cerebral concentrations and either prevent or facilitate recovery from a brain lesion induced by focal ischemia in rats. Aqueous and liposomal preparations of quercetin, fisetin and catechin were administered IP in a single dose and assessed in the brain by HPLC at 30 min, 1 h, 2 h and 4 h. Ischemic damage from focal middle cerebral artery occlusion was assessed spectrophotometrically with 2,3,5,-triphenylltetrazolium chloride (TTC).

Cytoprotection by neutral fraction of tannat red wine against oxidative stress-induced cell death.

Some of the beneficial effects of the Mediterranean diet on human pathologies have been attributed to red wine polyphenols. It has been postulated that the antioxidant activity of the latter would be also responsible for the cytoprotective capacity of red wine that has been reported in a few papers. Nevertheless, red wine shows a complex composition, and the active fraction is not known yet.

Cell culture protection and in vivo neuroprotective capacity of flavonoids.

Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studied in vivo. The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO).

Presynaptic involvement in the nicotine prevention of the dopamine loss provoked by 6-OHDA administration in the substantia nigra.

While nicotine, through stimulation of a specific sub-population of nicotinic acetylcholine receptors (nAChR) appears to protect cells in culture against a variety of insults, studies in vivo show controversial results. In a previous paper we have shown that in the 6-hydroxydopamine (6-OHDA) model of experimental parkinsonism, an intermittent administration schedule of nicotine (4 h before and 20, 44 and 68 h after 6-OHDA) was able to prevent the decrease of dopamine (DA) concentration in the corpus striatum (CS) provoked by the partial lesion of the substantia nigra (50% neuronal death after 6 micro g of 6-OHDA). To further analyze the mechanisms of nicotine effects, we performed a microdialysis study of striatal extracellular DA concentrations utilizing the nicotine administration schedule that was able to prevent DA decrease.