NMR-based Metabolomic Techniques Identify the Toxicity of Emodin in HepG2 Cells

Abstract

Emodin is a natural anthraquinone derivative that is present in various herbal preparations. The pharmacological effects of emodin include anticancer, hepatoprotective, anti-inflammatory, antioxidant and even antimicrobial activities. However, emodin also has been reported to induce hepatotoxicity, nephrotoxicity, genotoxicity and reproductive toxicity. The mechanism of emodin’s adverse effects is complicated and currently not well understood. This study aimed to establish a cell metabonomic method to investigate the toxicity of emodin and explore its potential mechanism and relevant targets. In the present study, metabonomic profiles of cell extracts and cell culture media obtained using the 1H NMR technique were used to assess emodin toxicity in HepG2 cells. Multivariate statistical analyses such as partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the metabolites that differed between the control and emodin groups. The results indicated that emodin resulted in differences in 33 metabolites, including acetate, arginine, aspartate, creatine, isoleucine, leucine and histidine in the cell extract samples and 23 metabolites, including alanine, formate, glutamate, succinate and isoleucine, in the cell culture media samples. Approximately 8 pathways associated with these metabolites were disrupted in the emodin groups. These results demonstrated the potential for using cell metabonomics approaches to clarify the toxicological effects of emodin, the underlying mechanisms and potential biomarkers. Our findings may help with the development of novel strategies to discover targets for drug toxicity, elucidate the changes in regulatory signal networks and explore its potential mechanism of action.

Metabolic Changes of Cholangiocarcinoma Cells in Response to Coniferyl Alcohol Treatment

“…As DMA is toxic to the cells, it might be excreted into the cell culture media. KKU-100 cells showed a decrease in the level of glutamine as in a similar report on emodin treatment for HepG2 cells [ 41 ]. The phosphorylation of ribose from inosine generates hypoxanthine by purine nucleoside phosphorylase (PNP) in a salvage pathway.…”

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

“…The different doses of emodin (25–400 μM) were applied to ejaculated human sperm, showed that sperm functions were inhibited by reducing sperm [Ca(2+)]i and prohibiting tyrosine phosphorylation in vitro ( Luo et al., 2015 ). In addition, it was found that 24 h emodin (100 μM) interrupted several metabolites and biological processes including amino acid metabolism, purine metabolism, and Krebs cycle disruption ( Chen et al., 2018 ). Since the ROS scavenging agent NAC can counteract the toxic effect of emodin, the increase in mitochondrial reactive oxygen production was also considered as an aspect of emodin toxicity ( Kolitsida and Abeliovich, 2017 ).…”

1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth

“…Metabolomics offers a trustable and effective tool to investigate the behaviour of biological systems by analysing their metabolic fingerprint 10 . Many applications have been described so far in the characterisation of the metabolic profile of plants 11 , 12 , as well as in the assessment of changes of the metabolic signature after a selected treatment, such as plant-derived medicines and conventional drugs 13 , or plant-derived metabolites 14 . Here, we aimed at further characterising the effect of Crithmum maritimum in HCC cells by using a metabolomic approach.…”