Radiation protection drugs are often accompanied by toxicity,even amifostine,which has been the dominant radio-protecting drug for nearly 30 years.Furthermore,there is no therapeutic drug for radiation-induced intesti...Radiation protection drugs are often accompanied by toxicity,even amifostine,which has been the dominant radio-protecting drug for nearly 30 years.Furthermore,there is no therapeutic drug for radiation-induced intestinal injury(RⅢ).This paper intends to find a safe and effective radioprotecting ingredient from natural sources.The radio-protecting effect of Ecliptae Herba(EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after137Cs irradiation.EHE components and blood substances in vivo were identified through UPLC-Q-TOF.The correlation network of “natural components in EHE-constituents migrating to blood-targets-pathways” was established to predict the active components and pathways.The binding force between potential active components and targets was studied by molecular docking,and the mechanism was further analyzed by Western blotting,cellular thermal shift assay(CETSA),and Ch IP.Additionally,the expression levels of Lgr5,Axin2,Ki67,lysozyme,caspase-3,caspase-8,8-OHd G,and p53 in the small intestine of mice were detected.It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection.Luteolin is a promising candidate for RⅢ.Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis.Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.展开更多
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-042,China).
文摘Radiation protection drugs are often accompanied by toxicity,even amifostine,which has been the dominant radio-protecting drug for nearly 30 years.Furthermore,there is no therapeutic drug for radiation-induced intestinal injury(RⅢ).This paper intends to find a safe and effective radioprotecting ingredient from natural sources.The radio-protecting effect of Ecliptae Herba(EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after137Cs irradiation.EHE components and blood substances in vivo were identified through UPLC-Q-TOF.The correlation network of “natural components in EHE-constituents migrating to blood-targets-pathways” was established to predict the active components and pathways.The binding force between potential active components and targets was studied by molecular docking,and the mechanism was further analyzed by Western blotting,cellular thermal shift assay(CETSA),and Ch IP.Additionally,the expression levels of Lgr5,Axin2,Ki67,lysozyme,caspase-3,caspase-8,8-OHd G,and p53 in the small intestine of mice were detected.It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection.Luteolin is a promising candidate for RⅢ.Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis.Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.
基金The National Natural Science Foundation of China( 3 0 170 164 ) Doctoral Foundation of the Ministry of Education( 2 0 0 0 0 3 0 70 8) Hi-tech Research and Development Program of China ( 863 Program :2 0 0 1AA2 460 12 ) and the Natural ScienceFound
