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
Objective:To investigate potential mechanisms of anti-atherosclerosis by berberine(BBR)using ApoE-/-mice.Methods:Eight 8-week-old C57BL/6J mice were used as a blank control group(normal),and 568-week-old AopE-/-mice w...Objective:To investigate potential mechanisms of anti-atherosclerosis by berberine(BBR)using ApoE-/-mice.Methods:Eight 8-week-old C57BL/6J mice were used as a blank control group(normal),and 568-week-old AopE-/-mice were fed a high-fat diet for 12 weeks,according to a completely random method,and were divided into the model group,BBR low-dose group(50 mg/kg,BBRL),BBR medium-dose group(100 mg/kg,BBRM),BBR high-dose group(150 mg/kg,BBRH),BBR+nuclear factor erythroid 2-related factor 2(NRF2)inhibitor group(100 mg/kg BBR+30 mg/kg ML385,BBRM+ML385),NRF2 inhibitor group(30 mg/kg,ML385),and positive control group(2.5 mg/kg,atorvastatin),8 in each group.After 4 weeks of intragastric administration,samples were collected and serum,aorta,heart and liver tissues were isolated.Biochemical kits were used to detect serum lipid content and the expression levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in all experimental groups.The pathological changes of atherosclerosis(AS)were observed by aorta gross Oil Red O,aortic sinus hematoxylin-eosin(HE)and Masson staining.Liver lipopathy was observed in mice by HE staining.The morphology of mitochondria in aorta cells was observed under transmission electron microscope.Flow cytometry was used to detect reactive oxygen species(ROS)expression in aorta of mice in each group.The content of ferrous ion Fe^(2+)in serum of mice was detected by biochemical kit.The mRNA and protein relative expression levels of NRF2,glutathione peroxidase 4(GPX4)and recombinant solute carrier family 7 member 11(SLC7A11)were detected by quantitative real time polymerase chain reaction(RT-q PCR)and Western blot,respectively.Results:BBRM and BBRH groups delayed the progression of AS and reduced the plaque area(P<0.01).The characteristic morphological changes of ferroptosis were rarely observed in BBR-treated AS mice,and the content of Fe^(2+)in BBR group was significantly lower than that in the model group(P<0.01).BBR decreased ROS and MDA levels in mouse aorta,increased SOD activity(P<0.01),significantly up-regulated NRF2/SLC7A11/GPX4 protein and mRNA expression levels(P<0.01),and inhibited lipid peroxidation.Compared with the model group,the body weight,blood lipid level and aortic plaque area of ML385 group increased(P<0.01);the morphology of mitochondria showed significant ferroptosis characteristics;the serum Fe^(2+),MDA and ROS levels increased(P<0.05 or P<0.01),and the activity of SOD decreased(P<0.01).Compared with BBRM group,the iron inhibition effect of BBRM+ML385 group was significantly weakened,and the plaque area significantly increased(P<0.01).Conclusion:Through NRF2/SLC7A11/GPX4 pathway,BBR can resist oxidative stress,inhibit ferroptosis,reduce plaque area,stabilize plaque,and exert anti-AS effects.展开更多
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.
基金Supported by the Henan Province Science and Technology Research Project(No.182102310093)。
文摘Objective:To investigate potential mechanisms of anti-atherosclerosis by berberine(BBR)using ApoE-/-mice.Methods:Eight 8-week-old C57BL/6J mice were used as a blank control group(normal),and 568-week-old AopE-/-mice were fed a high-fat diet for 12 weeks,according to a completely random method,and were divided into the model group,BBR low-dose group(50 mg/kg,BBRL),BBR medium-dose group(100 mg/kg,BBRM),BBR high-dose group(150 mg/kg,BBRH),BBR+nuclear factor erythroid 2-related factor 2(NRF2)inhibitor group(100 mg/kg BBR+30 mg/kg ML385,BBRM+ML385),NRF2 inhibitor group(30 mg/kg,ML385),and positive control group(2.5 mg/kg,atorvastatin),8 in each group.After 4 weeks of intragastric administration,samples were collected and serum,aorta,heart and liver tissues were isolated.Biochemical kits were used to detect serum lipid content and the expression levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in all experimental groups.The pathological changes of atherosclerosis(AS)were observed by aorta gross Oil Red O,aortic sinus hematoxylin-eosin(HE)and Masson staining.Liver lipopathy was observed in mice by HE staining.The morphology of mitochondria in aorta cells was observed under transmission electron microscope.Flow cytometry was used to detect reactive oxygen species(ROS)expression in aorta of mice in each group.The content of ferrous ion Fe^(2+)in serum of mice was detected by biochemical kit.The mRNA and protein relative expression levels of NRF2,glutathione peroxidase 4(GPX4)and recombinant solute carrier family 7 member 11(SLC7A11)were detected by quantitative real time polymerase chain reaction(RT-q PCR)and Western blot,respectively.Results:BBRM and BBRH groups delayed the progression of AS and reduced the plaque area(P<0.01).The characteristic morphological changes of ferroptosis were rarely observed in BBR-treated AS mice,and the content of Fe^(2+)in BBR group was significantly lower than that in the model group(P<0.01).BBR decreased ROS and MDA levels in mouse aorta,increased SOD activity(P<0.01),significantly up-regulated NRF2/SLC7A11/GPX4 protein and mRNA expression levels(P<0.01),and inhibited lipid peroxidation.Compared with the model group,the body weight,blood lipid level and aortic plaque area of ML385 group increased(P<0.01);the morphology of mitochondria showed significant ferroptosis characteristics;the serum Fe^(2+),MDA and ROS levels increased(P<0.05 or P<0.01),and the activity of SOD decreased(P<0.01).Compared with BBRM group,the iron inhibition effect of BBRM+ML385 group was significantly weakened,and the plaque area significantly increased(P<0.01).Conclusion:Through NRF2/SLC7A11/GPX4 pathway,BBR can resist oxidative stress,inhibit ferroptosis,reduce plaque area,stabilize plaque,and exert anti-AS effects.
