Disease relevance of NSC 11855

• In HepG2 human hepatoma cells, naringenin inhibits apolipoprotein B (apoB) secretion primarily by inhibiting microsomal triglyceride transfer protein and enhances LDL receptor (LDLr)-mediated apoB-containing lipoprotein uptake [1].
• We investigated renal excretion of naringin, naringenin, and its glucuronides after administration of 20 ml grapefruit juice (621 mumol/L naringin) per kilogram of body weight to six healthy adults [2].
• Several flavones inhibited the in vitro activation of aflatoxin B1 in a system employing umuC gene activation due to DNA damage in Salmonella typhimurium TA1535/pSK1002, with naringenin being as effective as any [3].
• Partially characterized aromatic metabolites with potential nod gene-inducing activity were detected among the products of naringenin degradation by Rhizobium leguminosarum bv. viciae [4].
• Multidrug resistance genes emrAB from Escherichia coli complemented an rmrA mutant from R. etli for resistance to high concentrations of naringenin [5].

Psychiatry related information on NSC 11855

• Naringenin, when administered to mice at 4.5 mg/kg body weight, significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance and the Y-maze test [6].
• These results suggest that naringenin may be a useful chemopreventive agent against Alzheimer's disease [6].

High impact information on NSC 11855

• Genistein and naringenin increased cellular accumulation of topotecan in K562/BCRP cells [7].
• Genistein and naringenin reversed neither P-glycoprotein-mediated vincristine resistance nor multidrug resistance-related protein 1-mediated VP-16 resistance [7].
• Inhibition of MEK1/2 significantly attenuated both the naringenin- and insulin-induced decrease in apoB100 secretion demonstrating a direct link between MAPK(erk) activation and apoB100 secretion [8].
• Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein B100 secretion by the citrus flavonoid naringenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes [8].
• Inhibition of MAPK kinase (MEK) 1/2 in HepG2 cells significantly attenuated the naringenin- and insulin-induced reduction in MTP expression [8].

Chemical compound and disease context of NSC 11855

• Following inoculation with Azorhizobium caulinodans ORS571 (pXLGD4), lateral root development of rice and colonization of lateral root cracks by bacteria were shown to be stimulated by the flavonoid naringenin [9].
• Four hitherto undescribed Clostridium strains capable of cleaving the C ring of quercetin, kaempferol, and naringenin at C-3-C-4 were isolated from the fecal flora of humans [10].
• The results of in vitro studies showed that 1 nM E2 increased (3- to 4-fold) the growth of MCF-7 human breast cancer cells, whereas 1-1000 nM naringenin had no effect on cell proliferation [11].
• In this report, we show that the grapefruit flava-none naringenin inhibited insulin-stimulated glucose uptake in proliferating and growth-arrested MCF-7 breast cancer cells [12].
• The in vitro and in vivo effects of two flavonons, naringenin (NG) and hesperitin (HP) on the proliferation rate of highly metastatic murine B16-F10 melanoma cell were investigated [13].

Biological context of NSC 11855

• In sharp contrast to insulin, naringenin did not induce tyrosine phosphorylation of IRS-1 [1].
• This agreement demonstrates that the observed kinetic protection results from the specific binding of naringenin to the active site [14].
• Following transcriptional activation of the bacterial nodulation genes using naringenin or bean seed exudate, we have isolated, purified, and characterized R. etli extracellular nodulation factors [15].
• We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation [1].
• Therefore, naringenin may prove useful for activating insulin-signaling pathways important for regulation of hepatocyte lipid homeostasis [8].

Anatomical context of NSC 11855

• We conclude that MAPK(erk) signaling in hepatocytes is critical for inhibition of apoB100 secretion by naringenin and insulin [8].
• Two prenyltransferases, naringenin 8-dimethylallyltransferase and LG 2"-dimethylallyltransferase, were localized in the plastids, whereas 8-dimethylallylnaringenin 2'-hydroxylase, which catalyzes the crucial step in the lavandulyl-group formation, was associated with the endoplasmic reticulum [16].
• In additional investigations, low concentrations (< 4 mumol/L) of naringenin glucuronides, but neither naringin nor naringenin were found in plasma samples from previous grapefruit juice interaction studies, and metabolization of naringin to naringenin occurred during 24 hours of incubation (37 degrees C) in three of five feces samples tested [2].
• Furthermore, in McA-RH7777-derived cell lines, naringenin reduced secretion of hapoB72 and hapoB100, which require significant assembly with lipid to be secreted, but did not reduce secretion of hapoB17, hapoB23, and hapoB48, which require only minimal lipidation [17].
• Inhibition of phenylalanine influx in guinea-pig small intestine by naringenin [proceedings] [18].

Associations of NSC 11855 with other chemical compounds

• The citrus flavonoid naringenin, like insulin, decreased MTP expression in HepG2 cells, resulting in inhibition of apoB100 secretion; however, the mechanism for naringenin is independent of insulin receptor substrate-1/2 [8].
• Expression of the polysaccharide was independent of the presence of a Sym plasmid or the nod gene inducer naringenin [19].
• After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives [20].
• Several flavonoids, especially naringenin and apigenin, markedly stimulated GSH transport by MRP1, suggesting they may be cotransported with this tripeptide [21].
• As a result, naringenin production (cross-reaction) by STS-P(375)G was close to 30% of resveratrol production [22].

Gene context of NSC 11855

• Insulin and naringenin induced PI3K-dependent increases in cytosolic and nuclear SREBP-1 and LDLr expression [1].
• The increased bioavailability caused by the concomitant intake of grapefruit juice results from the inhibition of intestinal cytochrome P450(CYP)3A4, but not hepatic CYP3A4 or colon CYP3A5, which probably involves the bioflavonoid naringenin and furanocoumarins [23].
• Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP [24].
• Moreover, naringenin selectively inhibited the transcription of Smad3, but not other Smads involved in TGF-beta1 signaling pathways [25].
• METHODS: In this study, reverse transcription-polymerase chain reaction and Western blot assays were used to investigate the inhibitory effect of naringenin on ECM formation induced by TGF-beta1 in the HSC-T6 cells [25].

Analytical, diagnostic and therapeutic context of NSC 11855

• The high concentration of derivatives of naringenin in certain citrus fruits may be of relevance to cancer chemoprevention involving those carcinogens that are activated by cytochrome P-450IIIA4 [3].
• Single enantiomers of naringenin were isolated by semipreparative HPLC and their CD spectra were measured and related to the absolute configuration by the exciton-coupling method [26].
• Hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activity was slightly low in naringin (5.0%)- and naringenin (15.0%)-fed rabbits, compared to control group [27].
• To measure naringin/naringenin absorption of a decoction prepared from the pericarps of Citrus grandis and to investigate the effect of honey on naringin/naringenin absorption, six healthy males received 200 mL decoctions of untreated and honey-treated Pericarpium Citri Grandis in a randomized crossover design [28].
• A microsomal preparation from irradiated parsley cell cultures catalyses the NADPH and dioxygen-dependent hydroxylation of (S)-naringenin [(S)-5, 7, 4'-trihydroxyflavanone] to eriodictyol (5, 7, 3', 4'-tetrahydroxyflavanone) [29].

References