In vitro reduction of rhein anthraquinone to rhein anthrone by rat cecal microflora and some intestinal bacterial strains

Abstract

After in vitro incubation of cecal content from CVL or gnotobiotic rats with rhein anthraquinone (1 mg g-1) for 18 h at 37 degrees, the anthraquinone was converted to rhein anthrone for 23.5 (SD +/- 3.4) per cent and 19.4 (+/- 4.7) per cent, respectively. Liquid cultures of some strictly anaerobic fecal bacteria of man and mouse incubated with rhein anthraquinone (62.5 micrograms ml-1) for 48 h at 37 degrees, revealed only small amounts of reduced substance. Although the underlying mechanisms of the differences in both conditions remain unclear, the experimental data accentuate the need for using cecal content when exploring the in vitro metabolism of anthranoids by the intestinal microflora. The conversion was chemically proven by derivatization of the anthrone with 4-nitroso-N-N-dimethylaniline in pyridine, followed by hydrolysis and identification of the released anthranoid by mass spectrometry. The in vitro reduction capacity of the cecal content of CVL rats was drastically decreased by oral administration to rats of different combinations of neomycin sulfate, metronidazole, bacitracin and Na-penicillin G. In these cases the conversion ranked between 0.2 per cent and 5.2 per cent the first day after administration. It is concluded that rhein anthraquinone in cecal content is reduced to the highly reactive and labile rhein anthrone, which accounts for the in vivo disappearance of dihydroxy-anthranoid equivalents in routine analysis after oral administration of anthraquinones to experimental animals.

Profiling the metabolic differences of anthraquinone derivatives using liquid chromatography/tandem mass spectrometry with data‐dependent acquisition

“…Therefore, investigations of their metabolism would be helpful in understanding the action mechanism for the therapeutic agents containing these compounds. To the best of our knowledge, earlier publications mainly adopted conventional means to investigate the metabolism of anthraquinone derivatives; metabolites were clarified by TLC, UV, MS and NMR after being separated and purified from massive biological matrices 5–9. However, it is not an exclusive approach to identify the metabolites.…”

Safety of hydroxyanthracene derivatives for use in food

“…Regarding the metabolism by bacteria of rhein, De Witte et al (1992) observed that in caecal contents of rats, rhein was reduced into rhein anthrone, by 23.5%. The in vitro reduction capacity of the caecal content of conventional rats was drastically decreased (to 0.2% and 5.2%) by oral administration to rats of antibiotics.…”

Metabolism and Pharmacokinetics of Anthranoids

“…In the case of rhein only 40% of the fecal ra dioactivity could be extracted, while emodin allowed some higher recoveries (75%). Since anthraquinones are stable substances and do not show radical formation, these data are explained on the basis of a reduction in vivo of the anthraquinone to the corresponding anthrone form, as proven for rhein anthraquinone [13,37] and danthron [10]. Thus, steril ized cecal content incubated with rhein an thraquinone did now show any conversion.…”

“…Moreover, a study with [l4C]emodin revealed the same absorption [32], The great difference between rhein anthraquinone and rhein anthrone is probably explained in terms of chemical stability and reactivity: rhein anthraquinone is a stable compound and a degradation to polyphenols, or a reac tion with unabsorbable substances present in the intestinal mass is unthinkable. However, a bacterial reduction of the anthraquinone takes place continuously [37], thereby slowly limiting its absorption. Another factor which inevitably reduces the absorption of rhein an throne, in contrast to rhein anthraquinone, is the limited amount of time the molecule spends in the intestinal tract, explained by the fact that rhein anthrone has a more outspoken pharmacological effect than the oxidized form [27].…”