Abstract：
Swietenia macrophylla King, belongs to the Meliaceae family, is a valuable medicinal plant and its fruits have been processed commercially to a variety of health foods. The seeds have long been known for their ethnomedicinal significance against these diseases. Swietenine (Swi) was isolated from S. macrophylla and could ameliorate inflammation and oxidative stress. In this study, HepG2 cells induced by H2 O2 were used to construct oxidative stress model in vitro. The aim of this study was to investigate the protective effect of Swi on H2 O2 induced oxidative injury in HepG2 cells and its molecular mechanism, and to explore the effect of Swi on liver injury in db/db mice and its possible mechanism. The results showed that Swi significantly inhibited HepG2 cells viability and reduced oxidative damage in a dose-dependent manner as evidenced by a range of biochemical analysis and immunoblotting study. Moreover, it induced the protein and mRNA expression of HO-1 together with its upstream mediator Nrf2 and activated the phosphorylation of AKT in HepG2 cells. LY294002, a PI3K/AKT inhibitor, significantly suppressed the Nrf2 nuclear translocation and HO-1 expression in H2 O2 induced HepG2 cells treated with Swi. In addition, RNA interference with Nrf2 significantly reduced the expression level of Nrf2 and HO-1 in the nucleus. Swi has a significant protective effect on cell damage in H2 O2 induced HepG2 cells by increasing the antioxidant capacity which is achieved through the AKT/Nrf2/HO-1 pathway. Additionally, in vivo, Swi could protect the liver of type 2 diabetic mice by improving lipid deposition in liver tissue and inhibiting oxidative stress. These findings indicated that Swi can be a promising dietary agent to improve type 2 diabetes.
摘要：
雨燕大叶王，属于蜜柳科,是一种有价值的药用植物，其果实已被商业加工成各种保健食品。长期以来，种子因其对这些疾病的种族意义而闻名。Swietenine（Swi）从大叶葡萄球菌中分离，可以改善炎症和氧化应激。在这项研究中,采用H2O2诱导的HepG2细胞体外构建氧化应激模型。本研究旨在探讨Swi对H2O2诱导的HepG2细胞氧化损伤的保护作用及其分子机制,探讨Swi对db/db小鼠肝损伤的影响及其可能机制。结果显示Swi以剂量依赖性方式显著抑制HepG2细胞活力并减少氧化损伤,如一系列生化分析和免疫印迹研究所证明的。此外，它诱导HO-1及其上游介质Nrf2的蛋白和mRNA表达，并激活HepG2细胞中AKT的磷酸化。LY294002，一种PI3K/AKT抑制剂，在Swi处理的H2O2诱导的HepG2细胞中，Nrf2核易位和HO-1表达显着抑制。此外,RNA干扰Nrf2显著降低Nrf2和HO-1在细胞核中的表达水平。Swi通过增加AKT/Nrf2/HO-1途径实现的抗氧化能力,对H2O2诱导的HepG2细胞损伤具有明显的保护作用。此外,在体内，Swi可以通过改善肝脏组织的脂质沉积和抑制氧化应激来保护2型糖尿病小鼠的肝脏。这些发现表明，Swi可以成为改善2型糖尿病的有前途的饮食剂。
