Disease relevance of C09265

• These data suggest that major features of rotenone-induced neurotoxicity are partially mediated by free radical formation and oxidative stress, and that fraxetin partially protects against rotenone toxicity affecting the main protection system of the cells against oxidative injury [1].
• Neuroprotective effect of fraxetin and myricetin against rotenone-induced apoptosis in neuroblastoma cells [2].

High impact information on C09265

• Of the remaining five, the most potent scavenger was fraxetin (7,8-dihydroxy-6-methoxycoumarin) with an IC50 (concentration producing 50% inhibition) of 2.3 microM in the cytochrome assay and 5.8 microM using NBT [3].
• Activity and expression of GPx were increased by rotenone and pre-treatment with fraxetin did not modify significantly these levels [1].
• When cells were preincubated with fraxetin, there was a decrease in the protein levels and activity of both MnSOD and catalase, in comparison with the rotenone treatment [1].
• The significant enhancement in HSP70 expression at mRNA and protein levels induced by fraxetin was observed by pre-treatment of cells 0.5 h before rotenone insult [1].
• These results demonstrated the protective action of fraxetin and suggest that it can reduce apoptosis, possibly by decreasing free radical generation in SH-SY5Y cells [4].

Biological context of C09265

• These results suggest that the natural antioxidants, such as fraxetin, may prevent the apoptotic death of dopaminergic cells induced by rotenone and mediated by oxidative stress [2].
• Taken together, this study suggested that intracellular GSH appeared to be an important factor in fraxetin-mediated cytoprotection against rotenone-toxicity in SH-SY5Y cells [5].
• Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment [6].
• Fraxetin at 10-100 muM inhibited the formation of ROS, cytochrome c release, activation of caspase-3 and 9, and suppressed the up-regulation of Bax, whereas no significant change occurred in Bcl-2 levels [5].
• Treatment of MG-63 cells with fraxetin not only inhibited anti-Fas IgM-induced apoptosis, but also blocked the synergetic effect of anti-Fas IgM with TNF-alpha or IL-1beta on cell death [7].

Anatomical context of C09265

• By means of alkaline phosphatase (ALP) activity and osteocalcin ELISA assay, we have shown that fraxetin exhibits a significant induction of differentiation in the human osteoblast-like cell line MG-63 [7].
• Our results indicated that fraxetin stimulated osteoblast differentiation at various stages (from osteoprogenitors to terminally differentiated osteoblasts) [8].

Associations of C09265 with other chemical compounds

• A phytochemical investigation of an ethanolic extract of the whole plant of Echites hirsuta (Apocynaceae) resulted in the isolation and identification of the flavonoids naringenin, aromadendrin (dihydrokaempferol), and kaempferol; the coumarin fraxetin; the triterpene ursolic acid; and the sterol glycoside sitosteryl glucoside [9].
• Urinary metabolites were analyzed by three-dimensional HPLC, and fraxetin-7-O-sulfate (2), fraxetin-7-O-beta-glucuronide (3), fraxetin (4), 6,7,8-trihydroxycoumarin (5), and fraxidin (6) were isolated [10].
• Liver SOD and GPx (total and Se-dependent) activities were not significantly affected by fraxetin, whereas they were increased in the brain compared with control animals [6].
• The aim of this paper was to study the influence of Fraxetin (7,8-dihydroxy-6-methoxv coumarin) treatment in a Drosophila melanogaster experimental model, analyzing several parameters in normal situations and instances of induced oxidative stress [11].
• The effects of various coumarins (i.e. esculetin, daphnetin and fraxetin) on the formation of the 5-lipoxygenase product, 5-HETE, and the cyclooxygenase product, HHT, were studied [12].

Gene context of C09265

• Bone morphogenetic protein-2 and -4 (BMP-2 and -4) mediates fraxetin-induced maturation and differentiation in human osteoblast-like cell lines [8].
• Induction of differentiation by fraxetin was associated with increased bone morphogenetic protein-2 (BMP-2) and BMP-4 productions [8].
• We concluded that the net effect of fraxetin treatment on endogenous antioxidant capacity suggests that this compound might provide an important resistance to, or protection against, free-radical-mediated events which contribute to degenerative diseases of ageing [6].

References