Differentiation induced by Achyrocline satureioides (Lam) infusion in PC12 cells.

Epidemiological studies have shown that flavonoid-rich plants induce beneficial health effects that are likely beyond their potent antioxidant capacity. Thus, the mechanisms by which Achyrocline satureioides (AS), a popular South American medicinal plant, protects cells and neurons in culture, are still unclear. In this sense, a recently described trophic capacity for flavonoids, similar to that evoked by growth factors, could be one of the mechanisms involved in AS cellular protection. Since this trophic activity causes differentiation of PC12 cells, the cell differentiation capacity of AS and some of its flavonoids were evaluated. PC12 cells were treated with AS infusion (10 or 20 microg/mL of total polyphenols), quercetin (Q) (12.5 or 25 microm), luteolin (L) (25 microm), Q + L (12.5 microm each one) or nerve growth factor (NGF) for 3 days. Four morphological parameters (percentage of cells with neurites longer than one cell body diameter, percentage of cells with neurites, average number of neurites per cell and percentage of fusiform cells) were explored. The AS infusion showed differentiation capacity on all parameters with similar potency when compared with NGF. Besides, AS was more potent than some of its constituent flavonoids: Q, L or their combination.

Cytoprotection by Achyrocline satureioides (Lam) D.C. and some of its main flavonoids against oxidative stress.

Epidemiological studies indicate that dietary antioxidants can influence the incidence of neurodegenerative diseases. Among them flavonoids have been proposed to be effective cytoprotectors. Consequently, herbs with a high concentration of these compounds such as Achyrocline satureioides, Ginkgo biloba and Epilobium parviflorum are of special interest. In this context a comparative study of the cytoprotective capacity of infusions from the three plants against an oxidative insult was performed. Hence, the cytoprotective activity of each infusion against H2O2 injury to PC12 cells was tested and the antioxidant capacity was assessed by the ABTS*+ radical bleaching assay. Free and glycosylated flavonoids contained in the infusions were identified by HPLC and the cytoprotective effect of some of these individual flavonoids was tested. The analysis of the flavonoid content of the infusions revealed different profiles. Epilobium parviflorum infusion showed the highest antioxidant capacity but only Achyrocline satureioides infusion proved to be cytoprotective. Moreover, the free flavonoids quercetin and luteolin contained in this infusion were also cytoprotective. In conclusion, the free radical scavenger capacity did not correlate with the cytoprotective profile of the infusions. The special mixture of unglycosylated Achyrocline satureioides flavonoids could be a clue to explain the unique effect of this plant.

Neuroprotection by flavonoids.

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 M) of H2O2 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.

Neuroprotection by flavonoids

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 æM) of H2O2 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.