Disease relevance of NSC57654

• The ability of these flavonoids to modulate apolipoprotein B (apoB) secretion and cellular cholesterol homeostasis was determined in the human hepatoma cell line, HepG2. apoB accumulation in the media decreased in a dose-dependent manner following 24-h incubations with naringenin (up to 82%, P < 0.00001) or hesperetin (up to 74%, P < 0.002) [1].
• The deleterious effect of hesperetin might be due to its toxicity or to the toxicity of its degradation product(s) as indicated by the inhibition of root growth [2].
• Preinduced Rhizobium with hesperetin at a concentration of 10 microM increased nodule number on average by 60.5% and dry matter accumulation by 14% in field pea at 17 degrees C, while it was 32% and 9% at 24 degrees C, respectively [3].
• In addition, hesperetin 7-O-(2",6"-di-O-alpha-rhamnopyranosyl)-beta-glucopyranoside (2) is reported for the first time from this plant and inhibits the influenza A virus [4].
• In pertussis or cholera toxin (PT or CT) pretreated adipocytes, the antilipolytic action of hesperetin was unaffected [5].

High impact information on NSC57654

• The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS) [6].
• The flavones apigenin and luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercitin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective [7].
• Pretreatment of RAW 264.7 with luteolin, luteolin-7-glucoside, quercetin, and the isoflavonoid genistein inhibited both the LPS-stimulated TNF-alpha and interleukin-6 release, whereas eriodictyol and hesperetin only inhibited TNF-alpha release [8].
• The objectives of this study were to develop methods allowing the analysis of naringenin and hesperetin from plasma and urine and to study their plasma kinetics and urinary excretion [9].
• Naringenin and hesperetin were bioavailable from the studied juices, but interindividual variation in bioavailability was remarkable [9].

Chemical compound and disease context of NSC57654

• When the excitotoxicity was induced by the glutamate receptor subtype-selective ligands, only the N-methyl-D-aspartic acid-induced toxicity was selectively and markedly inhibited by hesperetin [10].

Biological context of NSC57654

• Only butein and hesperetin showed inhibition of epinephrine-induced lipolysis, and their effect was dose-dependent [11].
• Naringenin and hesperetin displayed the strongest inhibitory effects (IC50 value of approximately 25 microM) [12].
• Exposure of fibroblasts to hesperetin led to concentration-dependent increases in the phosphorylation of ERK1/2 and was observed to restore peroxynitrite-mediated decreases in ERK1/2 phosphorylation [13].
• Hesperetin also manifested cytoprotection from cell damage induced by ONOO- and ROS [14].
• Similarly, averaged over two rhizobial strains, a 59% and 6% increase in nodule number and biomass production at 17 degrees C, and a 39% and 27% at 24 degrees C, were obtained from lentil inoculated with hesperetin-induced R. leguminosarum, respectively [3].

Anatomical context of NSC57654

• We propose that the protective potential of hesperetin in fibroblasts may be mediated both by intracellular scavenging of peroxynitrite and by modulation of fibroblast signalling [13].
• Antilipolytic action of hesperetin in rat adipocytes [5].
• Hesperetin (0.1 mM) significantly reversed the inhibitory effects of NA (1 microM) and high KCl (60 mM) on cyclic nucleotide (cAMP and cGMP) production in cultured rat aortic myocytes [15].
• Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in-vitro [16].
• CYP3A4 recombinant protein did not catalyze hesperetin demethylation, but showed similar metabolic profiles for the remaining compounds, as did human microsomes and recombinant CYP1A2, although the reaction rates in general were lower as compared to CYP1A2 [17].

Associations of NSC57654 with other chemical compounds

• This study investigated the vasorelaxant activity, superoxide radicals (O2(*-))-scavenging capacity and cyclic nucleotide phosphodiesterase (PDE)-inhibitory effects of hesperidin and hesperetin, two flavonoids mainly isolated from citrus fruits [15].
• We report that pre-treatment of fibroblasts with the citrus flavanone, hesperetin, prior to peroxynitrite exposure protects against peroxynitrite-mediated cytotoxicity [13].
• Four new monoterpenoids, shizonodiol, shizonol, and shizonepetosides D and E, have been isolated from SCHIZONEPETA TENUIFOLIA spikes along with the known flavonoids, diosmetin, hesperetin, and luteolin [18].
• The basal cyclic AMP levels and phosphodiesterase activities in intact adipocytes were unaltered by hesperetin [5].
• The interaction of the flavanone hesperetin with human skin fibroblasts (FEK4) has revealed the potential for metabolism to hesperetin glucuronide and its subsequent extrusion [19].

Gene context of NSC57654

• Hesperetin was not metabolized by human CYP1A2 or CYP3A4 [20].
• Modulation of peroxynitrite-induced fibroblast injury by hesperetin: a role for intracellular scavenging and modulation of ERK signalling [13].
• The citrus flavanones naringenin and hesperetin did not induce cell migration comparable with HGF in either cell type [21].
• As a result, hesperetin and nobiletin suppressed the phosphorylation of Akt-1, direct downstream effector of phosphatidylinositol 3-kinase (PI3-K) [22].
• The antilipolytic action of hesperetin in adenosine deaminase pretreated adipocytes was abolished [5].

Analytical, diagnostic and therapeutic context of NSC57654

• A simple, specific, precise, accurate, and robust HPLC assay for the simultaneous analysis of hesperetin and naringenin in human urine was developed and validated [23].
• RESULTS: The supplementation of hesperetin and its metabolites significantly lowered the plasma total cholesterol and triglyceride concentrations compared to the control group [24].
• Determination of hesperetin, cinnamic acid and nicotinic acid in propolis with micellar electrokinetic capillary chromatography [25].
• Hesperetin (5,7,3'-trihydroxyl-4'-methoxyl-flavanone) is an important bioactive compound in Chinese traditional medicine and has multiple biological and pharmacological activities [26].
• After oral administration of G-hesperidin or hesperidin to rats, hesperetin was detected in sera hydrolyzed with beta-glucuronidase, but it was not detectable in unhydrolyzed sera [27].

References