Neuroprotection by flavonoids

Abstract

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

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

“…In contrast, some studies showed that quercetin has beneficial effects in various in vivo models of cerebrovascular insults, possibly due to the increased permeability of the BBB in these animal models (49), which can facilitate delivery of quercetin into brain. In addition, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that this pharmaceutical preparation dosage form could help quercetin to cross the BBB in vivo (37). These studies show that quercetin itself might cross the BBB ineffectively, which could possibly be enhanced by modified pharmaceutical formulation.…”

Antiedema effects of proanthocyanidin on experimental traumatic brain edema

“…Phenolic antioxidants such as proanthocyanidin can inhibit the oxidation of lipids, carbohydrates, proteins and nucleic acids and can also protect against free radicals (6,12,22,32). They are polymers of flavonoid molecules that are widely available in vegetables, fruits, nuts, flowers, and seeds (especially grape seeds).…”

Anxiolytic Potential of Methanol Extract from Ageratum conyzoides Linn Leaves

“…20 Neuroprotective manifestation of flavonoids has been attributed to their general bioavailability and in vivo occurrence in the brain. 21 Quercetin, one of the flavonol found in large number of herbals, act as a monoamineoxidase A and B (MAO A and B) inhibitor. 22 Research has revealed that substances acting as MAO modulators elicit behavioral alterations in rodents by modifying monoamine level in brain, and consequently display an anxiolytic effect.…”