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.
Highlights
Drug-induced cytotoxicity is related to cell metabolism[13]
Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) methods were applied to maximize the distinction between groups, focusing on differences in metabolic variations, and to assess the correlations between the observed Nuclear magnetic resonance (NMR) results
A novel attempt was made to explore the possible mechanisms and relevant targets of emodin toxicity based on NMR non-targeted metabolomics
Summary
Drug-induced cytotoxicity is related to cell metabolism[13]. As a systemic approach, metabonomics adopts a “top-down” strategy to holistically reflect the function of organisms including terminal symptoms of metabolic network and understanding systemic metabolic changes caused by interventions[14]. Molecular profiling technologies, metabonomics provides new insights into the molecular basis of toxicity and provides a rich source of biomarkers that are urgently needed in 21st century toxicology research[15]. The metabolic profile of a whole organism does not provide relevant information about specific cell types under different conditions, which is crucial for creating a more holistic understanding of cell functions and for drug development[16]. Cell cultures may provide an alternative for understanding the specific metabolism of drug candidates[17]. A novel attempt was made to explore the possible mechanisms and relevant targets of emodin toxicity based on NMR non-targeted metabolomics. The objective was to establish a cell metabonomic method and identify biomarkers for investigating the toxic effects of emodin.
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