Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

作     者：Yuanyuan Wei Chen Gao Huiru Wang Yannan Zhang Jinhua Gu Xiuying Zhang Xuhao Gong Zhihui Hao Yuanyuan Wei;Chen Gao;Huiru Wang;Yannan Zhang;Jinhua Gu;Xiuying Zhang;Xuhao Gong;Zhihui Hao

作者机构：Innovation Centre of Chinese veterinary medicineCollege of Veterinary MedicineChina Agricultural UniversityNo.2 Yuanmingyuan West RoadBeijing 100193China Key Biology Laboratory of Chinese Veterinary MedicineMinistry of Agriculture and Rural AffairsBeijing 100193P.R.China National Center of Technology Innovation for Medicinal function of FoodNational Food and Strategic Reserves AdministrationBeijingChina China Institute of Veterinary Drug ControlBeijing 100081China 

出 版 物：《Journal of Animal Science and Biotechnology》 (畜牧与生物技术杂志（英文版）)

年 卷 期：2023年第14卷第4期

页      面：1418-1437页

核心收录：

学科分类：090603[农学-临床兽医学] 0905[农学-畜牧学] 09[农学] 0906[农学-兽医学] 

基　　金：supported by the Key Project at Central Government Level(2060302) National Natural Science Foundation of China(No.32172897)。 

主　　题：Acute and chronic liver injury Ferroptosis Mori fructus aqueous extracts Nrf2 Oxidative stress 

摘      要：Background Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective treatments.Mori fructus aqueous extracts(MFAEs)have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at present.Purpose To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying mechanism.Methods and results Mice were divided into 5 groups(n ps:contro=8)for acute(groups:control,0.3%CCl_(4),bifendate(BD),100 and 200 mg/kg MFAEs,7 d)and chronic(groul,10%CCl_(4),BD,100 and 200 mg/kg MFAEs,4 weeks)liver injury study.Each mouse was injected intraperitoneally with 10μL/g corn oil containing CCl_(4)expect the control group.HepG2 cells were used in vitro study.Eighteen communal components were identified by UPLC-LTQOrbitrap-MS.We utilized a mouse model for acute and chronic liver injury using CCl_(4)and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the liver.MFAEs activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1(Nrf2/HO-1)pathway and promoted the synthesis of the antioxidants glutathione(GSH),superoxidedismutase(SOD)and glutathione peroxidase(GSH-Px)that resulted in reduced levels of CCl_(4)-induced oxidative stress molecules including reactive oxygen species.These extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thus reducing the occurrence of liver fibrosis.Both in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 signaling.These effects were blocked in vitro by the addition of a specific Nrf2 inhibitor.Conclusion MFAEs inhibited oxidative stress,ferroptosis and inflammation of the liver by activating Nrf2 signal pathway and provided a significant protective effect against CCl_(4)-induced liver fibrosis.