Swietenine inhibited oxidative stress through AKT/Nrf2/HO‐1 signal pathways and the liver‐protective effect in T2DM mice: In vivo and in vitro study

• Published in: Environmental toxicology Vol. 38; no. 6; pp. 1292 - 1304
• Main Authors: Duan, Jingyu, Zhao, Yangqi, Pei, Feilong, Deng, Wenhao, He, Liangliang, Rao, Chengdian, Zhai, Yutong, Zhang, Chunping
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2023; Wiley Subscription Services, Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT; AKT protein; Animals; Apoptosis; Biochemical analysis; Cell viability; Cells; Damage; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diet; Gene expression; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Herbal medicine; Hydrogen peroxide; Immunoblotting; In vivo methods and tests; Lipids; Liver; Liver - metabolism; liver injury; Medicinal plants; Mice; Molecular modelling; Natural & organic foods; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NRF2 protein; Nuclear transport; Oxidation; Oxidative Stress; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; RNA-mediated interference; Seeds; Signal Transduction; swietenine; Translocation; type 2 diabetic mellitus; swietenine; type 2 diabetic mellitus; liver injury; AKT; oxidative stress
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23764

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 H2O2 were used to construct oxidative stress model in vitro. The aim of this study was to investigate the protective effect of Swi on H2O2 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 H2O2 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 H2O2 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.