Protective effect of coumarin-pi against t-BHP-induced hepatotoxicity by upregulating antioxidant enzymes via enhanced Nrf2 signaling

• Published in: Molecular and cellular biochemistry Vol. 475; no. 1-2; pp. 277 - 283
• Main Authors: Zhang, Jinxiu, Feng, Haiyan, Lv, Jianhua, Zhao, Liqiang, Zhao, Junxia, Wang, Li-an
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2020; Springer; Springer Nature B.V
• Subjects: Analysis; Annotations; Antioxidants; Apoptosis; Biochemistry; Biomedical and Life Sciences; Butyl hydroperoxide; Cardiology; Coumarin; Cysteine; Cytotoxicity; Encyclopedias; Gene expression; Genes; Genomes; Glutamate-cysteine ligase; Heme; Heme oxygenase (decyclizing); Hepatotoxicity; Life Sciences; Ligases; Medical Biochemistry; Metabolic pathways; Mushrooms; NAD; Oncology; Oxidative stress; Oxygenase; Quinones; Reactive oxygen species; Toxicity; Oxidative stress; HepG2 cells; Transcriptome sequencing; Coumarin-pi; Nrf2
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03880-x

Coumarin-pi, a new coumarin derivative isolated from the mushroom Paxillus involutus , has antioxidative activity, but the underlying mechanism against intracellular oxidative stress is still unclear. This study investigated its cytoprotective effects and the antioxidative mechanism in tert-butyl hydroperoxide (t-BHP)-induced HepG2 cells. The results demonstrated that coumarin-pi suppressed t-BHP-stimulated cytotoxicity, cell apoptosis, and generation of reactive oxygen species (ROS). Additionally, coumarin-pi promoted nuclear factor erythroid 2-related factor 2 (Nrf2) expression and upregulated the protein expression of antioxidantenzymes, including heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidase (NQO1), glutamyl cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase regulatory subunit (GCLM). After coumarin-pi treatment, transcriptome sequencing and bioinformatic analysis revealed that 256 genes were differentially expressed; interestingly, only 20 genes were downregulated, and the rest of the genes were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation were used to identify changes in metabolic pathways. Collectively, the results presented in this study indicate that coumarin-pi has a protective effect against t-BHP-induced cellular damage and oxidative stress.