Nonenzymatic reduction of thymoquinone in physiological conditions.
Thymoquinone (TQ) is the bioactive constituent of the volatile oil of Nigella sativa L. and has been shown to exert antioxidant antineoplastic and anti-inflammatory effects. During the study of its possible mechanism of action, we found that TQ reacts chemically (i.e. nonenzymatically) with glutathione (GSH), NADH and NADPH. A combination of liquid chromatography/UV-Vis spectrophotometry/Mass spectrometry analyses was used to identify the products of these reactions. The reaction that occur in physiological conditions indicates the formation of only two products, glutathionyl-dihydrothymoquinone after rapid reaction with GSH, and dihydrothymoquinone (DHTQ) after slow reaction time with NADH and NADPH. Measurement of the antioxidant activity of reduced compounds against organic radicals such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) also revealed a potential scavenging activity for glutathionyl-dihydrothymoquinone similar to that of DHTQ. Under our experimental conditions, TQ shows lower scavenging activities than glutathionyl-dihydrothymoquinone and DHTQ; it is very interesting to observe that the reduced compounds apparently show an antioxidant capacity equivalent to Trolox. The results indicate a possible intracellular nonenzymatic metabolic activation of TQ dependent on GSH, NADH or NADPH that may represent a "cellular switch" able to modulate cellular antioxidant defences.
Khalife
K H
KH
Department of Biology MCA, University of Camerino, Camerino, Italy.
Lupidi
G
G
D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D016227:Benzoquinones / Q000378:metabolism* / Q000494:pharmacology; D052160:Benzothiazoles / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000378:metabolism; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010851:Picrates; D013451:Sulfonic Acids / Q000378:metabolism
D000975:Antioxidants; D016227:Benzoquinones; D052160:Benzothiazoles; D001713:Biphenyl Compounds; D002839:Chromans; D016166:Free Radical Scavengers; D006834:Hydrazines; D010851:Picrates; D013451:Sulfonic Acids; D009243:NAD; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D009249:NADP; C004931:1,1-diphenyl-2-picrylhydrazyl; D005978:Glutathione; C003466:thymoquinone; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid