The high morbidity, high socioeconomic costs and lack of specific treatments are key factors that define the relevance of brain pathology for human health and the importance of research on neuronal protective agents. Epidemiological studies have shown beneficial effects of flavonoids on arteriosclerosis-related pathology in general and neurodegeneration in particular. Flavonoids can protect the brain by their ability to modulate intracellular signals promoting cellular survival. Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin) showed a marked cytoprotective capacity in in vitro experimental conditions in models of predominantly apoptotic death such as that induced by medium concentrations (200 µM) of H 2 O 2 added to PC12 cells in culture. Nevertheless, quercetin did not protect substantia nigra neurons in vivo from an oxidative insult (6-hydroxydopamine), probably due to difficulties in crossing the blood-brain barrier. On the other hand, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that preparations that help to cross the blood-brain barrier may be critical for the expression of the effects of flavonoids on the brain. The hypothesis is advanced that a group of quercetin-related flavonoids could become lead molecules for the development of neuroprotective compounds with multitarget anti-ischemic effects. Key words Brain vascular pathology and oxidative stressIt is known that brain pathology in the form of cerebrovascular and neurodegenerative disease is a leading cause of death all over the world, with an incidence of about 2/1000 and an 8% total death rate (1-3). Moreover, stroke and dementia are a source of high individual and family suffering mainly because of the lack of efficient therapeutic alternatives. The latter motivates research efforts to identify the mechanisms of neuronal death and to discover new compounds to control them.Neuronal death in stroke is a complex event involving failure of metabolic processes, excitotoxicity, loss of calcium homeostasis and oxidative stress, among other factors (4). During ischemic stroke, a decrease in metabolic energy in the form of ATP affecting membrane ionic pumps leads to an increase in intracellular Ca 2+ and Na + concentrations and to increased glutamate
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. Antioxidation, modulation of signaling cascades and gene expression as well as anti-inflammation appear as the main protective mechanisms and mitochondria are a likely main target mediating the preventive actions against oxidative stress. Flavones and flavonols re-establish the redox regulation of proteins, transcription factors and signaling cascades that are otherwise inhibited by elevated oxidative stress. The final survival or death of the neuron depends on flavone and flavonol concentrations, time of exposure and, mainly, metabolic and oxidative neuronal circumstances. Neuroprotection appears to be linked to specific structural motifs, beyond those involved in antioxidation. By themselves or as templates for synthetic compounds, flavone and flavonol molecules show potential as multi-targeted therapeutic tools for protecting the brain. Nonetheless, more research needs to be done on the correlation of potential beneficial effects of flavones and flavonols and their mechanisms of action.
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. Afterwards the skin was exposed to 1 h of UV irradiation from a known source. The production of the hydroxyl (OH.) radical was assessed in the skin after UV by measuring 2,3-dyhydroxybenzoic acid (2,3-DHBA), produced by the hydroxylation of sodium salicylate, previously injected intracutaneously (i.c.) in the irradiated areas. The UV provoked a marked increase in 2,3-DHBA that was significantly decreased by the AS cosmetic preparation. The EP extract did not show any effect on 2,3-DHBA production. It is concluded that the cosmetic preparation containing the AS extract is able to scavenge OH. production likely to be due to the presence of high concentrations of flavonoid aglycones such as quercetin, luteolin and 3-O-methylquercetin.
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