Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach

Abstract

The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. In the present study, we aimed to profile entire endogenous metabolites in a biological system using a multisample integrated metabolomics strategy. Our findings offered additional insights into the molecular mechanism of the DBR-induced hepatotoxicity. We identified different metabolites from rat plasma, urine, and feces by employing gas chromatography-mass spectrometry in combination with multivariate analysis. In total, 55 metabolites distributed in 33 metabolic pathways were identified as being significantly altered in DBR-treated rats. Correlation network analysis revealed that the hub metabolites of hepatotoxicity were mainly associated with amino acid, bile acid, purine, pyrimidine, lipid, and energy metabolism. As such, DBR affected the physiological and biological functions of liver via the regulation of multiple metabolic pathways to an abnormal state. Notably, our findings also demonstrated that the multisample integrated metabolomics strategy has a great potential to identify more biomarkers and pathways in order to elucidate the mechanistic complexity of toxicity of traditional Chinese medicine.

LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice

“…The liver plays a crucial role in amino acid metabolism, it is responsible for a large part of the overall amino acid synthesis and catabolism. The alteration of amino acid metabolism has recently is related to liver injury ( Zhao et al., 2017 ), and increased or decreased amino acids were as potential hepatotoxicity biomarkers ( An et al., 2020 ). Similarly, compared with the control group, L-glutamic acid was decreased both in low- and high-dose groups ( Figure 4 ), suggesting that OA disturbed amino acid metabolism.…”

Biomarker identification and pathway analysis of rheumatoid arthritis based on metabolomics in combination with ingenuity pathway analysis

“…Additionally, PCA score plot was also employed to assess data quality, as it provides the standard deviation (SD) distribution of the peak area for the QC samples [50]. The CVs of the QC samples were within ±2SD range, indicating good instrument reproducibility during the entire batch analysis (Figure 2B) [51].…”

Metabolomics Used in Herb-Induced Liver Injury

“…It can reveal the dynamic mechanism of PM causing liver injury. Cui et al [13]. Discovered that 55 metabolites distributed in 33 metabolic pathways were identified as being…”