Disease relevance of juglone

• Dicumarol increased the toxicity of 1,4-naphthoquinone dramatically and somewhat the toxicity of 2-hydroxy-1,4- naphthoquinone, whereas 5-hydroxy-1,4-naphthoquinone and 5,8-dihydroxy-1,4-naphthoquinone toxicity increased only slightly [1].
• The mode of action was studied by analyzing the inactivation kinetics and the nature of products of the reaction of E. coli parvulin and its Cys69Ala variant with juglone [2].
• In addition, histological examination of all tumors produced during promotion with juglone revealed the presence of both kerathoacanthomas and sebaceous squamous cell carcinomas [3].
• Finally, under optimal promoting conditions, juglone was very effective at supporting the conversion of papillomas to carcinomas (carcinoma/papilloma ratio of 0.35) [3].
• Growth of Helicobacter pylori was inhibited by the quinones, idebenone, duroquinone, menadione, juglone, and coenzyme Q(1) at low concentrations of 0.8 to 3.2 mug/ml [4].

High impact information on juglone

• The apicomplexan parasite Toxoplasma gondii is highly susceptible to oxidative stress caused by tert-butyl-hydroperoxide, juglone, and phenazine methylsulfate with IC(50) in the nanomolar range [5].
• Similar to human Pin1 and yeast Ess1, it exhibits catalytic activity toward substrates containing (Thr(P)/Ser(P))-Pro peptide bonds and comparable inhibition kinetics with juglone [6].
• Here, we describe the isolation of MdPin1, a Pin1 homologue from the plant species apple (Malus domestica) and show that it has the same phosphorylation-specific substrate specificity and can be inhibited by juglone in vitro, as is the case for Pin1 [7].
• The chemical juglone (5-hydroxy-1,4-naphthoquinone) inhibited the interaction, suggesting that peptidyl-prolyl isomerization may mediate auxin-induced SHY2/IAA3 protein turnover [8].
• The AK1 worms (extrachromosomal and integrated lines) were found to be much more resistant to internal (juglone) and external (hypoxanthine/xanthine oxidase) oxidative stress than wild-type C.elegans worms [9].

Chemical compound and disease context of juglone

• Mechanisms of toxicity of 2- and 5-hydroxy-1,4-naphthoquinone; absence of a role for redox cycling in the toxicity of 2-hydroxy-1,4-naphthoquinone to isolated hepatocytes [10].

Biological context of juglone

• Three of the benzoquinones are uncouplers in the order juglone greater than maesoquinone greater than embelin, while maesanin is an inhibitor of electron transport and oxidative phosphorylation [11].
• The percentage increase in K+ channel inactivation rate and the degree of drug induced block was independent of membrane potential, K+ channel block by juglone fully developed within 4 minutes and was not removable by washing with drug free extracellular solution [12].
• The natural toxin juglone causes degradation of p53 and induces rapid H2AX phosphorylation and cell death in human fibroblasts [13].
• Our results show that juglone has multiple effects on cells such as the induction of DNA damage, inhibition of transcription, reduction of p53 protein levels and the induction of cell death [13].
• Previous studies have proposed that disruption of electron transport functions in mitochondria and chloroplasts contribute to observed growth reduction in species exposed to juglone [14].

Anatomical context of juglone

• As a control, keratinocytes loaded with DCFH were incubated in the dark with either exogenously added H(2)O(2) or 5-hydroxy-1,4-naphthoquinone (juglone), which redox cycles to generate superoxide (and H(2)O(2)) [15].
• An antenna-based origin for the quenching was verified experimentally by the observation that addition of the antenna quencher 5-hydroxy-1,4-naphthoquinone to thylakoids under Fm conditions resulted in decay kinetics and modeled kinetic parameters very similar to those observed under Fsat conditions in the absence of added quinone [16].
• Furthermore, juglone inhibits mRNA synthesis in human fibroblasts in a dose-dependent manner [13].
• Blocking of n-type K+ channels by juglone is in concert with its depolarizing effect on human lymphocytes [12].
• The two zinc porphyrins were capable of mediating CT degradation at rates comparable to those observed with the M. thermophila exudates; however, juglone was only capable of very slow CT transformation [17].

Associations of juglone with other chemical compounds

• Starting from menadione, plumbagin, and juglone, three distinct series of 1,4-naphthoquinones (NQ) were synthesized as potential inhibitors of TR from Trypanosoma cruzi (TcTR) [18].
• Juglone (5-hydroxy-1,4-naphthoquinone) and plumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone) are yellow pigments found in black walnut (Juglans regia) [19].
• In the present study, in vitro scission of isolated DNA was induced upon juglone reduction by glutathione and Fe(II) ions, however, not by xanthine oxidase or cytochrome c reductase [20].
• The inhibition of phosphatidylinositol-3-kinase (PtdIns-3-kinase), protein kinase C and c-Src protein tyrosine kinase by a series of halogenated naphthoquinones and quinoline quinones related to the plant-derived naphthoquinones juglone and methyljuglone, which inhibit protein kinase C, has been investigated [21].
• The toxic naphthoquinone juglone (5-hydroxy-1,4-naphthoquinone) is efficiently degraded by the ligninolytic fungus Pleurotus sajor-caju, as demonstrated by the total bleaching within 9 d of a conventional liquid culture medium supplemented with 0.6 mM juglone [22].

Gene context of juglone

• This response may have been triggered by DNA damage since juglone induced a rapid and strong phosphorylation of H2AX in all phases of the cell cycle [13].
• Walnut extract inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils [23].
• Activity measurements showed only PQ served as a substrate for camel lens zeta-crystallin, while juglone, 1,4-NQ, and 1,2-NQ were inhibitors [24].
• Induction of quinone reductase and glutathione transferase in rat tissues by juglone and plumbagin [25].
• It is shown that NADPH, NAD(P)H:quinone reductase, juglone, cyt b561, the peroxidase interacting with cyt b561, and H2O2, in this order, constitute an artificial electron transfer chain in which cyt b561 is indirectly reduced by NADPH and indirectly oxidized by H2O2 [26].

Analytical, diagnostic and therapeutic context of juglone

• Juglone, a toxic compound found in all parts of plants of the walnut tree family Jugans, was evaluated as the possible toxin involved in black walnut shaving-associated laminitis in the horse [27].
• The metabolism and disposition of 14C-labelled juglone in male F344 rats following oral, intravenous and dermal administration were studied [28].
• Gas chromatography/mass spectrometry of aqueous extracts of heartwood, bark and nuts of black walnut identified juglone in the bark and nuts, but not in the heartwood [29].
• For this purpose, we optimized the simultaneous analysis of the most commonly occurring naphthoquinones (1,4-naphthoquinone, lawsone, juglone and plumbagin) by high performance liquid chromatography coupled with diode array detector (HPLC-DAD) [30].

References