Aloe emodin induces hepatotoxicity by activating NF-κB inflammatory pathway and P53 apoptosis pathway in zebrafish.
The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate the hepatotoxicity mechanism of AE, the zebrafish Tg (fabp10: EGFP) was used as an animal model in vivo. The pathological sections of zebrafish liver were analyzed to observe the histopathological changes and Sudan black B was used to study whether there were inflammatory reactions in zebrafish liver or not. Then TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptotic signal of zebrafish liver cells, finally the mRNA expression levels as well as the protein expression levels of the targets in NF-κB and P53 pathways in zebrafish were measured by quantitative Real-Time PCR (qRT-PCR) and western blot. Molecular docking results showed that AE could successfully dock with all the targets of NF-κB and P53 pathways, and the docking scores of most of the targets were equal to or higher than that of the corresponding ligands. Pathological sections showed AE could cause zebrafish liver lesions and the result of Sudan black B staining revealed that AE blackened the liver of zebrafish with Sudan black B. Then TUNEL assay showed that a large number of dense apoptotic signals were observed in AE group, mainly distributed in the liver and yolk sac of zebrafish. The results of qRT-PCR and western blot showed that AE increased the mRNA and protein expression levels of pro-inflammatory and pro-apoptotic targets in NF-κB and P53 pathways. AE could activate the NF-κB inflammatory pathway and the P53 apoptosis pathway, and its hepatotoxic mechanism was related to activation of NF-κB-P53 inflammation-apoptosis pathways.
['Quan|Yunyun|Y|', 'Gong|Lihong|L|', 'He|Junlin|J|', 'Zhou|Yimeng|Y|', 'Liu|Meichen|M|', 'Cao|Zhixing|Z|', 'Li|Yunxia|Y|', 'Peng|Cheng|C|']
D000818:Animals D030801:Animals, Genetically Modified D000880:Anthraquinones D017209:Apoptosis D056486:Chemical and Drug Induced Liver Injury D007249:Inflammation D008099:Liver D062105:Molecular Docking Simulation D016328:NF-kappa B D016133:Polymerase Chain Reaction D012333:RNA, Messenger D015398:Signal Transduction D016159:Tumor Suppressor Protein p53 D015027:Zebrafish D029961:Zebrafish Proteins
Aloe emodin Hepatotoxicity Zebrafish P53 pathway NF-κB pathway