Emodin is a natural anthraquinone derivative that occurs in many Chinese medicinal herbs.

Emodin is one of the main active compounds in many Chinese traditional herbs. Due to its potential toxic effect on the liver, the possible injury mechanism needs to be explored. In the present study, we investigated liver injury mechanisms of emodin on rats by the technology of proteomics. Firstly, 4530 proteins were identified from the liver of rats treated with emodin by label free proteomics. Inside, 892 differential proteins were selected, presenting a downward trend. Bioinformatics analysis showed that proteins interfered with by emodin were mainly involved in oxidation-reduction biological processes and mitochondrial metabolic pathways, such as mitochondrial fatty acid b-oxidation, citric acid cycle, and oxidative phosphorylation, which were further confirmed by western blot. The decrease in maximal respiration, ATP production, spare respiratory capacity, and coupling efficiency and increase in proton leakage were detected by seahorse XFe 24 analyzer, which confirmed the damage of mitochondrial function. The down-regulated expressions in antioxidant proteins were verified by western blot and a significant increase of ROS levels were detected in emodin group, which showed that emodin disrupted redox homeostasis in livers. Molecular docking revealed that the main targets of emodin might be acadvl and complex IV. Generally, emodin could induce oxidative stress in livers by directly targeting acadvl/complex IV and inhibiting fatty acid b-oxidation, citric acid cycle, and oxidative phosphorylation taken place in mitochondria.

Objective: Investigate the active ingredients and underlying hypolipidemic mechanisms of Danhe granule (DHG). Methods: The lipid-lowering effect of DHG was evaluated in hyperlipidemic hamsters induced by a high-fat diet. The ingredients absorbed into the blood after oral administration of DHG in hamsters were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A systems pharmacology approach incorporating target prediction and network construction, gene ontology (GO) enrichment and pathway analysis was performed to predict the active compounds and map the compounds-targets-disease network. Real-time polymerase chain reaction (RT-PCR) and Western blot were utilized to analyze the mRNA and protein expression levels of predicted targets. Results: DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. Sixteen ingredients absorbed into blood after oral administration of DHG were identified as the possible components interacted with targets. Moreover, 65 potential targets were predicted after targets intersection and compounds-targets-disease network mapping. Then, compounds-targets-pathways network mapping revealed that six active compounds (emodin, naringenin, etc.) compounds could interact with 10 targets such as sterol regulatory element binding protein (SREBP) 1c, SREBP-2 and peroxisome proliferation-activated receptor (PPAR) a, regulate three lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, and further affect lipid metabolic processes including fatty acid biosynthesis, low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARa, liver X receptor alpha (LXRa),

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