Abstract
Emodin is the main component of traditional Chinese medicines including rhubarb, Polygonum multiflorum, and Polygonum cuspidatum. It has confirmed hepatotoxicity and may be the main causative agent of liver damage associated with the above-mentioned traditional Chinese medicines. However, current research does not explain the mechanism of emodin in hepatotoxicity. In this study, L02 cells were used as a model to study the mechanism of emodin-induced hepatocyte apoptosis using quantitative proteomics, and the results were verified by Western blot. A total of 662 differentially expressed proteins were discovered and analyzed using Gene Ontology (GO) and pathway enrichment analysis. The results show that the oxidative phosphorylation pathway is highly represented. Abnormalities in this pathway result in impaired mitochondrial function and represent mitochondrial damage. This result is consistent with mitochondria membrane potential measurements. Analysis of differentially expressed proteins revealed that emodin mainly affects oxidative phosphorylation pathways by inhibiting the function of the mitochondrial respiratory chain complexes; the mitochondrial respiratory chain complex activity assay result also confirmed that emodin could inhibit the activity of all mitochondrial complexes. This results in an increase in caspase-3, a decrease in mitochondrial membrane potential (MMP,) an increase in reactive oxygen species (ROS), and disorders in ATP synthesis, etc., eventually leading to mitochondrial damage and hepatocyte apoptosis in vitro.
Highlights
Emodin is an anthraquinone mainly found in traditional Chinese medicines such as rhubarb, Polygonum multiflorum, and Polygonum cuspidatum
46.7% of L02 cell growth and 67.9% of L02 cell growth at a concentration of 100 μM. This result is consistent with previous studies that showed that emodin has strong hepatotoxicity [16]
To ensure the accuracy and consistency of our proteomics research, dose selection mainly refers to the concentration of emodin in plasma and liver after oral administration of Polygonum cuspidatum or other herbs which contain emodin
Summary
Emodin is an anthraquinone mainly found in traditional Chinese medicines such as rhubarb, Polygonum multiflorum, and Polygonum cuspidatum. It has many pharmacological activities, such as anti-cancer and anti-inflammatory effects, constipation relief, liver protection, and anti-aging effects [1,2,3,4,5,6]. Previous in vitro studies have shown that emodin can cause apoptosis in normal human L02 cells [13,16]. These studies employed high-content analysis, which confirmed that
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