Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuropro...Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.展开更多
Objective:To analyze the correlation between serum Nrf2 and GPX4 activity levels with coronary heart disease(CHD)and the severity of coronary artery disease,and to explore the role of ferroptosis mediated by its signa...Objective:To analyze the correlation between serum Nrf2 and GPX4 activity levels with coronary heart disease(CHD)and the severity of coronary artery disease,and to explore the role of ferroptosis mediated by its signaling pathway in the progression of CHD.Methods:A total of 540 patients suspected of CHD were selected for coronary angiography,of which 360 patients were diagnosed with CHD.The activity levels of Nrf2 and GPX4 in the serum of CHD patients were detected by ELISA,and the differences in the activities of Nrf2 and GPX4 in the presence or absence of CHD were statistically analyzed.Western blot detection of Nrf2 protein expression of peripheral blood mononuclear cells(PBMCS)in the control(CON)and CHD groups(90 cases each).The expression and significance of its signaling pathway in CHD patients were analyzed.Results:The activity levels of Nrf2 and GPX4 in the CHD group were lower than those in the CON group(P<0.05),and the expression levels of Nrf2 in PBMCs of the two groups were detected by Western blot.The protein expression level of Nrf2 in the CHD group(0.25±0.05)was down‑regulated compared with CON group(0.87±0.16)(P<0.05),indicating that Nrf2 protein expression level was low in CHD patients.Pearson correlation analysis showed that serum Nrf2 and GPX4 levels were negatively correlated with Gensini score(Nrf2:r=‑0.347,P<0.001;GPX4:r=-0.423,P=0.001).Nrf2 and GPX4 were negatively correlated with TG(Nrf2:r=-0.284,P<0.001;GPX4:r=-0.275,P=0.001),Nrf2 and GPX4 levels were negatively correlated with LDL(Nrf2:r=-0.418,P<0.001)0.05;(GPX4:r=-0.426,P<0.05),Nrf2 and GPX4 levels were positively correlated with HDL(Nrf2:r=0.318,P<0.05;GPX4:r=0.428,P<0.05),and Nrf2 was positively correlated with GPX4(r=0.456,P<0.01).Conclusion:The ferroptosis pathway mediated by the Nrf2‑GPX4 signaling pathway is closely related to the degree of coronary artery disease and the pathogenesis of CHD,and its mechanism may be related to the down‑regulation of the Nrf2‑GPX4 signaling pathway.展开更多
基金supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian LiTibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yang YXAnti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Lu QX.
文摘Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.
基金National Natural Science Foundation of China(No.81970313)Key Natural Science Project of Bengbu Medical College(No.2020byzd072)Bengbu Medical College Natural Science Key Project(No.2020byzd109)。
文摘Objective:To analyze the correlation between serum Nrf2 and GPX4 activity levels with coronary heart disease(CHD)and the severity of coronary artery disease,and to explore the role of ferroptosis mediated by its signaling pathway in the progression of CHD.Methods:A total of 540 patients suspected of CHD were selected for coronary angiography,of which 360 patients were diagnosed with CHD.The activity levels of Nrf2 and GPX4 in the serum of CHD patients were detected by ELISA,and the differences in the activities of Nrf2 and GPX4 in the presence or absence of CHD were statistically analyzed.Western blot detection of Nrf2 protein expression of peripheral blood mononuclear cells(PBMCS)in the control(CON)and CHD groups(90 cases each).The expression and significance of its signaling pathway in CHD patients were analyzed.Results:The activity levels of Nrf2 and GPX4 in the CHD group were lower than those in the CON group(P<0.05),and the expression levels of Nrf2 in PBMCs of the two groups were detected by Western blot.The protein expression level of Nrf2 in the CHD group(0.25±0.05)was down‑regulated compared with CON group(0.87±0.16)(P<0.05),indicating that Nrf2 protein expression level was low in CHD patients.Pearson correlation analysis showed that serum Nrf2 and GPX4 levels were negatively correlated with Gensini score(Nrf2:r=‑0.347,P<0.001;GPX4:r=-0.423,P=0.001).Nrf2 and GPX4 were negatively correlated with TG(Nrf2:r=-0.284,P<0.001;GPX4:r=-0.275,P=0.001),Nrf2 and GPX4 levels were negatively correlated with LDL(Nrf2:r=-0.418,P<0.001)0.05;(GPX4:r=-0.426,P<0.05),Nrf2 and GPX4 levels were positively correlated with HDL(Nrf2:r=0.318,P<0.05;GPX4:r=0.428,P<0.05),and Nrf2 was positively correlated with GPX4(r=0.456,P<0.01).Conclusion:The ferroptosis pathway mediated by the Nrf2‑GPX4 signaling pathway is closely related to the degree of coronary artery disease and the pathogenesis of CHD,and its mechanism may be related to the down‑regulation of the Nrf2‑GPX4 signaling pathway.
