Metabolomic Responses of Human Hepatocytes to Emodin, Aristolochic Acid, and Triptolide: Chemicals Purified from Traditional Chinese Medicines

Abstract

The present study was undertaken to investigate the metabolic responses of human liver cells HL-7702 on chemicals purified from traditional Chinese medicine: emodin, triptolide, and aristolochic acid. Cytotoxicity tests demonstrated a dose-dependent toxic effect of emodin, triptolide, and aristolochic acid on HL7702 cells for 48 h. Emodin (14 μM), aristolochic acid (12 μg/mL), or triptolide (18 nM) was individually administrated to HL7702 and cell samples were collected after 48 h for metabolites extraction and analysis. Pattern recognition analysis reflected the significant difference in metabolic profiles between chemical-treated groups and the control group. Finally, eight metabolites including N1 -acetylspermidine, Glu Gly, N-undecanoylglycine, C16 sphinganine, sphinganine, glutathione, l-palmitoylcarnitine, and elaidic carnitine were detected as potential common biomarkers. Three pathways including sphinganine metabolism, fatty acid oxidation, and oxidative stress were identified. Our findings indicated that metabolomics would be an efficient approach to understand the molecular mechanism of hepatotoxicity induced by chemicals.

Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction

“…Analysis of serum samples from rats in the control and emodin groups indicated that emodin induced liver injury (Yang et al, 2018). Previous studies have also found that emodin induced liver injury in vivo and in vitro to some extent (Li et al, 2012;Zhang et al, 2010;Liu et al, 2015b;Ma et al, 2015;Jiang et al, 2017), similar to our observation.…”

Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption

“…Elevated levels of metabolites from these groups are associated with altered fatty acid oxidation/metabolism and disease. [30][31][32] Analysis of the fecal metabolome by GC/LC-MS separated patients with IBS from control individuals ( Figure 3C), again without difference among the clinical IBS subtypes ( Supplementary Figure 7). Machine learning identified 158 fecal metabolites predictive of IBS (AUC, 0.686; sensitivity, 0.737; specificity, 0.476) ( Supplementary Table 7), which included the amino acids L-alanine, L-arginine, tyrosine, Lphenylalanine; dodecanedioic acid, an indicator of fatty acid oxidation defects, 33 and 2 purine nucleosides, adenosine and inosine, previously reported as biomarkers of IBS.…”

Lactobacillus brevis Alleviates DSS-Induced Colitis by Reprograming Intestinal Microbiota and Influencing Serum Metabolome in Murine Model

“…However, these changes exhibited opposite trends in the DSS vs. LB-DSS comparison. The N1-acetylspermidine metabolites, which are related to amino acid metabolism and oxidative stress in cells, are polyamines derived from ornithine and methionine and play an important role in cell membrane stability, biosynthesis of signaling molecules, and cell growth and differentiation (Ramot et al, 2010; Liu et al, 2015). Arachidonic acid is the main precursor of eicosanoid mediators, and the abundance of this metabolite is greatly increased after cell activation (Calder, 2011).…”