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Isoflurane, a common volatile anesthetic, has been widely used to provide general anesthesia in operations. However, exposure to isoflurane may cause widespread neurotoxicity in the developing animal brain. Fraxetin, a natural coumarin derivative extracted from the bark of Fraxinus rhynchophylla, possesses versatile pharmacological properties including anti-oxidative, anti-inflammatory, and neuroprotective effects. However, the effect and action mechanism of fraxetin on neurotoxicity induced by isoflurane are unknown. Reactive oxygen species (ROS) generation, cell viability, lactate dehydrogenase (LDH) release, and apoptosis were estimated by 2',7'-dichlorofluorescin-diacetate (DCFH-DA) staining, MTT, LDH release, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining assays, respectively. The protein levels of light chain 3 (LC3)-I, LC3-II, p62, protein kinase B (Akt), and phosphorylated Akt (p-Akt) were detected by western blot analysis. Isoflurane induced ROS, LDH release, apoptosis, and autophagy, but inhibited the viability in HT22 cells, which were overturned by fraxetin or ROS scavenger N-acetyl-L-cysteine. Fraxetin suppressed isoflurane-induced PI3K/Akt inactivation in HT22 cells. PI3K/Akt inactivation by LY294002 resisted the effects of fraxetin on isoflurane-induced autophagy and autophagy-modulated neurotoxicity in HT22 cells. In conclusion, fraxetin suppressed ROS-dependent autophagy by activating the PI3K/Akt pathway to inhibit isoflurane-induced neurotoxicity in hippocampal neuronal cells.

International audience; Iron (Fe) is a major micronutrient and is required for plant growth and development. Nongrass species have evolved a reduction-based strategy to solubilize and take up Fe. The secretion of Fe-mobilizing coumarins (e.g. fraxetin, esculetin and sideretin) by plant roots plays an important role in this process. Although the biochemical mechanisms leading to their biosynthesis have been well described, very little is known about their cellular and subcellular localization or their mobility within plant tissues. Spectral imaging was used to monitor, in Arabidopsis thaliana, the in planta localization of Fe-mobilizing coumarins and scopolin. Molecular, genetic and biochemical approaches were also used to investigate the dynamics of coumarin accumulation in roots. These approaches showed that root hairs play a major role in scopoletin secretion, whereas fraxetin and esculetin secretion occurs through all epidermis cells. The findings of this study also showed that the transport of coumarins from the cortex to the rhizosphere relies on the PDR9 transporter under Fe-deficient conditions. Additional experiments support the idea that coumarins move throughout the plant body via the xylem sap and that several plant species can take up coumarins present in the surrounding media. Altogether, the data presented here demonstrate that coumarin storage and accumulation in roots is a highly complex and dynamic process.

The aim of this work was to study the structure-activity relationships of the antioxidant activity of natural coumarins isolated from four Korean medicinal plants (1-17) and four purchased coumarins (18-21). The free radical scavenging and lipid peroxidation assays revealed that five phenolic coumarins, scopoletin (1), aesculetin (2), fraxetin (3), umbelliferone (18) and daphnetin (19), possessed considerable antioxidant activities. The coumarins having a catechol group, 2, 3 and 19, showed significant free radical scavenging activity and inhibitory effects on lipid peroxidation, indicating that the catechol group significantly contributed to the antioxidant activities of coumarins. In contrast, the sugar moiety markedly reduced the activities of coumarin glycosides. The results also demonstrate that the alpha-pyrone ring of coumarins significantly enhanced the capacity of inhibiting oxidative reactions of coumarins.

This study was conducted to investigate the influence of treatment with fraxetin (7,8-dihydroxy-6-methoxy coumarin), on the lifespan and longevity of Drosophila melanogaster (both sexes), introducing the treatment at different ages and comparing the differences in a situation of stress or not. Different groups were established to determine the maximum longevity (the maximum amount of time that an individual can survive) and the time of life was measured of an homogeneous population until the death of the last individual. This parameter is genetically determined; and is related to the metabolic rate and it appears unchangeable by most environmental factors. From this parameter, the average longevity was determined, establishing an average maximum age between the different subgroups for the same group of treatment, considering the maximum life reached in every subgroup. The third parameter studied is the lifespan (time that 50% of individuals survive), it is affected by both genetic and environmental factors. The object of this investigation was to establish the influence of stress (provoked by an assay of flying­capacity) in the lifespan of the flies, and to study how treatment can protect individuals against induced stress. The survival values of the individuals submitted to an assay of flying capacity, during its development until the death of the last individual was evaluated. The three parameters for these individuals were established. Fraxetin administration did not reduce the lifespan in male Drosophila, but prolonged the lifespan and longevity in female flies, especially with a 2-week treatment, both in normal conditions and in a stress situation (the assay of flying capacity was considered as the response to a stress situation). Male Drosophila in a stress situation presented with a reduction of flying capacity, related to age, and also of the maximum life. Whereas, females only presented changes in the flying parameter, without modifications in the lifespan. © 1998 John Wiley & Sons, Ltd.

From Jatropha cilliata M. Arg., a Peruvian medicinal plant, isoorientin and orientin were isolated as anxiolytic components by using the isolation guide of anti-conflict effect in mice. Several related flavonoids were also tested for this effect. Another bioassay-guided isolation using the acetic acid-induced writhing method gave a coumarin compound, fraxetin, as an analgesic principle.

Purpurasol 1, a 6,7,8-trioxygenated coumarin, isolated from Pterocaulon purpurascens (Asteraceae) and Haplophyllum obtusifolium (Rutaceae), was synthesized for the first time by a three-step synthesis starting from the natural coumarin fraxetin. This synthesis confirmed unambiguously the structure of purpurasol 1 and obtusifol.

5 coumarins used in perfumery, cosmetics, therapeutic ointments or occurring naturally were investigated by Freund's complete adjuvant technique (FCAT) in guinea pigs to determine their contact sensitizing potency. 4-Methylesculetin was also studied. Esculetin, dihydrocoumarin and daphnetin were found to be moderate to strong sensitizers, while fraxetin was nearly and 7-methylcoumarin completely inactive. The results corroborate the hypothetical view that only those coumarins having a catecholic disubstitution in the benzene ring, e.g., esculetin, 4-methylesculetin, daphnetin, can become sensitizers on the basis that they are capable of forming ortho-quinones under oxidizing conditions.