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. 2019 Mar 20;8(3):263.
doi: 10.3390/cells8030263.

Inhibition of Mitochondrial Complex Function-The Hepatotoxicity Mechanism of Emodin Based on Quantitative Proteomic Analyses

Longfei Lin  1 , Yuling Liu  2 , Sai Fu  3 , Changhai Qu  4 , Hui Li  5 , Jian Ni  6
Affiliations

Inhibition of Mitochondrial Complex Function-The Hepatotoxicity Mechanism of Emodin Based on Quantitative Proteomic Analyses

Longfei Lin et al. Cells. .

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.

Keywords: complex; emodin; hepatotoxicity; mitochondrial; proteomic.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Cell proliferation results by Cell Counting Kit-8 (CCK-8) assay after emodin administrated for 24 h and 48 h (means ± SD, n = 3).
Figure 2
Figure 2
The differentially expressed proteins filter through a volcano map.
Figure 3
Figure 3
The hierarchical clustering of total protein (A) and differentially expressed proteins (B). * K1,2,3 are the three control groups; G11-1, -2, -3 are the three administered groups (n = 3).
Figure 4
Figure 4
The results of Gene Ontology (GO) enrichment analysis of the differentially expressed proteins.
Figure 5
Figure 5
The results of pathway analysis of the differentially expressed proteins.
Figure 6
Figure 6
The expression of seven protein in L02 cells after treated with emodin for 48 h, (means ± SD, n = 3).
Figure 7
Figure 7
The changes of mitochondrial membrane potential (MMP) in L02 cells after treatment with emodin for 24 h and 48 h under different concentrations, (means ± SD, n = 3).
Figure 8
Figure 8
The results of mitochondrial respiratory chain complex activity assay (means ± SD, n = 3).
Figure 9
Figure 9
The possible hepatotoxicity signal pathway of apoptosis induced by emodin.
See this image and copyright information in PMC

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