Dynamic metabolic profiling of urine biomarkers in rats with alcohol‑induced liver damage following treatment with Zhi‑Zi‑Da‑Huang decoction.

Abstract

Alcoholic liver disease (ALD) is a leading cause of liver‑associated morbidity and mortality. Zhi‑Zi‑Da‑Huang decoction (ZZDHD), a traditional Chinese medicine formula, has been frequently used to treat or alleviate the symptoms of the various stages of ALD. To identify metabolic changes and the ZZDHD mechanism of action on ALD, potential urine biomarkers involved in the effects of ZZDHD were identified. Additionally, dynamic metabolomic profiles were systematically analyzed using nuclear magnetic resonance (NMR) spectroscopy in conjunction with statistical analysis. Alcohol administration to experimental rats disrupted multiple metabolic pathways, including methionine, gut bacterial, energy and amino acid metabolism. However, ZZDHD relieved certain effects of alcohol on the metabolism and regulated changes in potential characteristic biomarkers, including dimethylglycine, hippurate, lactate and creatine. The present study investigated time‑dependent metabolomic changes in the development of alcohol‑induced liver injury, including the effect of ZZDHD intervention. These findings elucidated important information regarding the metabolic responses to the protective effects of ZZDHD. 1H NMR‑based metabolomics method a reliable and useful tool for determining the metabolic progression of alcohol‑induced liver injury and elucidating the underlying mechanisms of the effect of traditional Chinese medicine formulas. This study also demonstrated that NMR‑based metabolomics approach is a powerful tool for understanding the molecular basis of pathogenesis and drug intervention processes.