Cholestatic liver injury model of bile duct ligation and the protection of Huang-Lian-Jie-Du decoction by NMR metabolomic profiling

Abstract

Cholestatic liver injury has been increasingly recognized as a cause for high morbidity and mortality of some diseases in humans. This model could be established by bile duct ligation (BDL), which led to the toxic accumulation of bile acids in animals, resulting in cholestatic liver injury. In this study, rats were intragastrically administrated with an extract of Huang-Lian-Jie-Du decoction once a day for seven consecutive weeks to study its therapeutic effect. Serum and urine samples were collected and subjected to ¹H NMR-based metabolomic analysis. Perturbations on energy metabolism, amino acid metabolism, gut bacteria metabolism and oxidative stress were observed in BDL rats. The metabolomic pattern showed a distinct biphasic feature of the BDL model. Most of these metabolic disturbances occurred in the acute phase (week 1) were greatly attenuated in the long run. HLJDD ameliorated the disturbed metabolism throughout this model, showing bilateral adjustment of some metabolites varied in opposite direction in the two phases. This study demonstrated that ¹H NMR-based metabolomic approach is a powerful and feasible tool to study the pathological changes of a disease model dynamically and holistically and for the understanding of the therapeutic effects of complex Chinese herbal medicine formulae.