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

Author:

Duan Jingyu1,Zhao Yangqi1,Pei Feilong1,Deng Wenhao1,He Liangliang1,Rao Chengdian1,Zhai Yutong1,Zhang Chunping12ORCID

Affiliation:

1. School of Pharmacy Xuzhou Medical University Xuzhou People's Republic of China

2. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou People's Republic of China

Abstract

AbstractSwietenia 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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine

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