The aim of this study was to establish the potential effect of Laurus nobilis ethanolic extract on improving insulin sensitivity and protecting liver cells from apoptosis, mitochondrial dysfunction, oxidative stress (OS), and inflammation; all of which considered as major alterations occurring during insulin resistance (IR) as well as diabetes onset, in hyperinsulinemic and hyperglycemic-induced HepG2 cell line. Thereby, L. nobilis ethanolic extract has been first chemically characterized using LC-MS/MS technique. Subsequently, HepG2 cells were pre-treated with an optimal concentration of L. nobilis ethanolic extract for 24 h, and then, subjected to 30 mM D-glucose and 500 nM insulin mixture for another 24 h in order to induce hyperinsulinemia and hyperglycaemia (HI/HG) status. Several parameters such as biocompatibility, hepatotoxicity, reactive oxygen species (ROS), mitochondrial transmembrane potential, dynamics, and metabolism, multicaspase activity, glucose uptake, in addition to genes and proteins expression levels were investigated. The obtained results showed that the bioactive extract of Laurus nobilis increased the number of living cells and their proliferation rate, significantly attenuated apoptosis by modulating pro-apoptotic pathways (p21, p53 and Bax genes), allowed a relative normalization of caspases-activity, and decreased the expression of inflammatory markers including c-Jun, NF-κB and Tlr4 transcripts. L. Nobilis ethanolic extract reduced considerably total intracellular ROS levels in challenged HepG2 cells, and regulated the mitochondrial OXPHOS pathway, demonstrating the potential antioxidant effect of the plant. Ethanolic plant extract increased insulin sensitivity, since an elevated expression of master transcripts responsible for insulin sensitivity including IRS1, IRS2, INSR was found. Taken together, obtained data suggest that L. nobilis ethanolic extract offers new insights in the development of potential antioxidant, insulin sensitizing as well as hepatoprotective drugs.

本研究的目的是确定月桂乙醇提取物对提高胰岛素敏感性和保护肝细胞免于凋亡、线粒体功能障碍、氧化应激 (OS) 和炎症的潜在作用；所有这些都被认为是在高胰岛素血症和高血糖诱导的 HepG2 细胞系中发生在胰岛素抵抗 (IR) 和糖尿病发作期间发生的重大变化。因此，首次使用 LC-MS/MS 技术对L. nobilis乙醇提取物进行了化学表征。随后，HepG2 细胞用最佳浓度的L. nobilis预处理乙醇提取物 24 小时，然后再加入 30 mM D-葡萄糖和 500 nM 胰岛素混合物 24 小时，以诱导高胰岛素血症和高血糖 (HI/HG) 状态。除基因和蛋白质表达水平外，还研究了几个参数，例如生物相容性、肝毒性、活性氧 (ROS)、线粒体跨膜电位、动力学和代谢、多半胱天冬酶活性、葡萄糖摄取。获得的结果表明，月桂的生物活性提取物增加了活细胞的数量和增殖率，通过调节促凋亡途径（p21、p53和Bax ）显着减弱了细胞凋亡。基因），使半胱天冬酶活性相对正常化，并降低炎症标志物的表达，包括c-Jun、NF-κB和Tlr4转录物。L. Nobilis乙醇提取物显着降低了受到攻击的 HepG2 细胞中的总细胞内 ROS 水平，并调节了线粒体 OXPHOS 途径，证明了植物的潜在抗氧化作用。乙醇植物提取物增加了胰岛素敏感性，因为发现了负责胰岛素敏感性的主转录物（包括IRS1、IRS2、INSR ）的表达升高。总之，获得的数据表明L. nobilis乙醇提取物为开发潜在的抗氧化剂、胰岛素增敏剂和保肝药物提供了新的见解。