- In Vitro and in Vivo Studies of the Electrophilicity of Physcion and its Oxidative Metabolites
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Physcion (1,8-dihydroxy-3-methoxy-6-methyl-9,10-anthracenedione) is a bioactive component found in Polygoni Multiflori Radix (PMR), which has been widely used as traditional Chinese medicine. Unfortunately, studies showed hepatotoxicity of PMR during its clinical use. The mechanisms of its toxic action remain unknown. The major objectives of this study were to characterize oxidative metabolites of physcion in vitro and in vivo and to determine the electrophilicity of the parent compound and its oxidative metabolites. Five oxidative metabolites (M1-M5) were detected in rat liver microsomal incubations after exposure to physcion, and the formation of the metabolites was NADPH dependent. M1-M4 were monohydroxylation metabolites, and M5 was O-demethylation metabolite. A total of three N-acetylcysteine (NAC) conjugates (M6-M8) were observed in rat liver microsomes fortified with NAC as a trapping agent. M6 was derived from M4 conjugated with a molecule of NAC; M7 and M8 originated from parent compound physcion adducted with a molecule of NAC, respectively. M1-M8 were also observed in urine of rats given physcion. HLM incubations produced four oxidative metabolites and two NAC conjugates. The structures of M3, M7, and M8 were characterized by LC-Q-TOF MS and NMR. Recombinant P450 enzyme incubations demonstrated that CYPs2C19, 1A2, 2B6, and 3A4 were mainly involved in hydroxylation of physcion. The metabolism study assisted us to better understand the mechanisms of physcion-induced hepatotoxicity.
- Qin, Xiaotong,Peng, Ying,Zheng, Jiang
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- Characterization of emodin metabolites in Raji cells by LC-APCI-MS/MS
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A rapid, simple, and sensitive liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) method was developed for the identification and quantification of emodin metabolites in Raji cells, using aloe-emodin as an internal standard. Analyses were performed on an LC system employing a Cosmosil 5C18 AR-II column and a stepwise gradient elution with methanol-20 mM ammonium formate at a flow rate of 1.0 mL/min operating in the negative ion mode. As a result, the starting material emodin and its five metabolites were detected by analyzing extracts of Raji cells that had been cultivated in the presence of emodin. The identification of the metabolites and elucidation of their structures were performed by comparing their retention times and spectral patterns with those of synthetic samples. In addition to the major metabolite 8-O-methylemodin, four other metabolites were assigned as ω-hydroxyemodin, 3-O-methyl-ω-hydroxyemodin, 3-O-methylemodin (physcion), and chrysophanol.
- Koyama, Junko,Takeuchi, Atsuko,Morita, Izumi,Nishino, Yu,Shimizu, Maki,Inoue, Munetaka,Kobayashi, Norihiro
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p. 7493 - 7499
(2011/02/23)
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- Chemische Studien ueber natuerliche Anthrachinone. II. Synthese von Citreoroseine, Fallacinol und Fallacinal
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The meltingpoint and infrared spectrum of synthesized 1,6,8-trihydroxy-3-hydroxymethylanthraquinone (II) were identical with those of citreoroseine (I) .Synthesis of 1,3-diacetoxy-3-bromomethyl-6-methoxyanthraquinone (VIII) was established.And fallacinal (V) could be prepared by oxidation of fallacinol (IV).Keywords - Penicillium citreo-roseum DIERCKX; Xanthoria fallax (HEPP.) ARN.; citreorosein; fallacinol; fallacinal; 3-formyl-1,6,8-trihydroxyanthraquinone
- Hirose, Yoshio,Suehiro, Yoshihisa,Furukawa, Yumiko,Murakami, Takao
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p. 4186 - 4188
(2007/10/02)
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