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.

香豆素-pi，一种从香菇Paxillus involutus中分离出的新香豆素衍生物具有抗氧化活性，但针对细胞内氧化应激的潜在机制仍不清楚。这项研究调查了其在叔丁基过氧化氢（t-BHP）诱导的HepG2细胞中的细胞保护作用和抗氧化机制。结果表明，香豆素-pi抑制了t-BHP刺激的细胞毒性，细胞凋亡和活性氧（ROS）的产生。此外，香豆素-pi促进了核因子红系2相关因子2（Nrf2）的表达，并上调了抗氧化剂酶的蛋白表达，包括血红素加氧酶-1（HO-1），NAD（P）H：醌氧化酶（NQO1），谷氨酰半胱氨酸连接酶催化亚基（GCLC）和谷氨酸-半胱氨酸连接酶调节亚基（GCLM）。经过香豆素pi处理后 转录组测序和生物信息学分析表明，共有256个基因被差异表达。有趣的是，只有20个基因被下调，其余基因被上调。使用基因本体论（GO）和《京都议定书基因与基因组百科全书》（KEGG）功能注释来识别代谢途径的变化。总体而言，本研究中提出的结果表明香豆素-pi对t-BHP诱导的细胞损伤和氧化应激具有保护作用。