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
Background:Radiotherapy,a primary approach in cancer treatment,damages normal cells while targeting cancer cells.Therefore,it is crucial to identify drugs with minimal side effects,high reliability,and radioprotective...Background:Radiotherapy,a primary approach in cancer treatment,damages normal cells while targeting cancer cells.Therefore,it is crucial to identify drugs with minimal side effects,high reliability,and radioprotective effects to develop novel radiotherapy strategies.Hemerocallis citrina extracts(HCE),which are derived from plants with medicinal and culinary applications,possess antioxidative and anticancer properties.Methods:In this study,we investigated the radioprotective effects of HCE on LO2 cells exposed to radiation to determine whether these effects were mediated through the nuclear factor erythroid 2–related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway.Results:Cell proliferation experiments demonstrated the radioprotective effect of HCE on LO2 cells.Western blot analysis revealed that HCE regulated B-cell lymphoma protein 2-associated X,Cleaved-caspase 3,and B-cell lymphoma protein 2,thereby inhibiting radiation-induced apoptosis,which was consistent with the flow cytometry results.Conclusions:Moreover,the detection of ferroptosis-related markers indicated that HCE alleviated radiation-induced ferroptosis in LO2 cells through the nuclear factor erythroid 2–related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway.These findings provide a theoretical basis for the radioprotective effects of HCE on LO2 cells and offer new insights into the development of radioprotective drugs.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supported by the Natural Science Foundation of Hunan Province(2021JJ30592)Health Commission Scientific Research Project of Hunan Province(D202309037942)+1 种基金Key Research Project of Education Department of Hunan Province(19A429)National Natural Science Foundation of China(81272994).
文摘Background:Radiotherapy,a primary approach in cancer treatment,damages normal cells while targeting cancer cells.Therefore,it is crucial to identify drugs with minimal side effects,high reliability,and radioprotective effects to develop novel radiotherapy strategies.Hemerocallis citrina extracts(HCE),which are derived from plants with medicinal and culinary applications,possess antioxidative and anticancer properties.Methods:In this study,we investigated the radioprotective effects of HCE on LO2 cells exposed to radiation to determine whether these effects were mediated through the nuclear factor erythroid 2–related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway.Results:Cell proliferation experiments demonstrated the radioprotective effect of HCE on LO2 cells.Western blot analysis revealed that HCE regulated B-cell lymphoma protein 2-associated X,Cleaved-caspase 3,and B-cell lymphoma protein 2,thereby inhibiting radiation-induced apoptosis,which was consistent with the flow cytometry results.Conclusions:Moreover,the detection of ferroptosis-related markers indicated that HCE alleviated radiation-induced ferroptosis in LO2 cells through the nuclear factor erythroid 2–related factor 2-cystine–glutamate antiporter/glutathione peroxidase 4 pathway.These findings provide a theoretical basis for the radioprotective effects of HCE on LO2 cells and offer new insights into the development of radioprotective drugs.
