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

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 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.

3,4′,5-Trimethoxy-trans-stilbene ameliorates hepatic insulin resistance and oxidative stress in diabetic obese mice through insulin and Nrf2 signaling pathways

“…In the context of T2DM, the PI3K/Akt pathway is known to perform a key role in activating Nrf2 in response to oxidative stress. [58][59][60] It facilitates the dissociation of Nrf2 from Keap1, safeguarding Nrf2 from degradation. Simultaneously, it enhances the stability of Nrf2 and enables its translocation into the nucleus.…”

Natural product Swietenine improve the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Akt/GSK-3β/Nrf2 signaling pathway

“…According to reports, Swi can be accessed through NF-κB/NLRP3/Caspase-1 signaling pathway reduces in ammation and oxidative stress and improves DN [46] . In HepG2 cells induced by H 2 O 2 , Swi has antioxidant capacity through AKT/Nrf2/HO-1 signaling pathway, signi cantly inhibits Nrf2 nuclear translocation and HO-1 expression, reduces in ammatory response, and protects the liver of type 2 diabetes mice [47] .In this study, we showed for the rst time that Swietenine signi cantly improved STZ/HFD-induced diabetic nephropathy and HG-induced MPC-5 cell death in vivo and in vitro by inhibiting the occurrence of oxidative stress and ferroptosis. Meanwhile, our research has found that the possible mechanism of these effects is that Swi activates through activation the Akt/GSK-3β/Nrf2 signaling pathway improves ferroptosis in DN while promoting antioxidant stress.…”

“…More and more evidence shows that Swi is a natural product with a variety of pharmacological activities, such as anti diabetes, improving in ammation, antioxidation, anti-bacterial, anti-tumor, etc. It has been con rmed that Swi can reduce blood sugar, improve the in ammatory response of liver, kidney and pancreas in the process of diabetes, and oxidative stress [21][22][23] . This indicates that it may be a potential drug of choice for the treatment of DN.…”