The Microbial Biotransformation of Soy Genistein Significantly Enhances Its Trapping Capacities of Reactive Carbonyl Metabolites

Abstract

Abstract Objectives Carbonyl stress is the abnormal accumulation of carbonyl metabolites, such as methylglyoxal (MGO) and acrolein (ACR) that leads to increased modification of protein, lipids and DNA, and contributes to cell and tissue dysfunction resulting in aging and diseases, such as diabetes, cardiovascular diseases and neurodegenerative diseases. Carbonyl stress is caused by an imbalance in the formation and metabolism of carbonyl metabolites and also by increased exposure to exogenous carbonyl species. In vitro studies have shown that dietary flavonoids have the capacities to detoxify reactive carbonyl metabolites. However, whether flavonoids can trap carbonyl metabolites in vivo and whether biotransformation especially microbial metabolism limits the trapping capacities of flavonoids remain virtually unknown. The objective of this study is to use soy genistein as an example to test the impacts of bioavailability and biotransformation on the in vivo trapping capacities of RCS by genistein. Methods Chemically, we synthesized the MGO and ACR conjugates of genistein as authentic standards. In mice, we oral gavaged 200 mg/kg genistein or vehicle to mice. Urine and feces were collected in metabolic cages for 24 h. The urine samples from genistein treated mice were also used to prepare the RCS conjugates of genistein metabolites. Using LC tandem mass and the high-resolution accurate mass, we searched and identified the formation of genistein metabolites and their corresponding RCS conjugates. The RCS conjugates of genistein and its metabolites were also quantified using the synthetic standards. Results We found that 1) absorbed genistein trapped endogenous MGO and ACR by forming mono-RCS adducts and eventually be excreted into mouse urine; 2) absorbed genistein could produce active phase I metabolite, orobol, to scavenge endogenous MGO and ACR; and 3) considerable amounts of microbial metabolites of genistein displayed enhanced anti-RCS capacity both in the body and in the gut, compared to genistein. Conclusions Our findings demonstrate that in vivo anti-RCS ability of dietary polyphenols cannot be reflected solely based on their in vitro ability. The bioavailability and biotransformation of individual polyphenols especially gut microbiome contribute to in vivo anti-RCS ability of dietary polyphenols. Funding Sources N/A.