Discovery of the radio-protecting effect of Ecliptae Herba,its constituents and targeting p53-mediated apoptosis in vitro and in vivo

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.

Advances on marine-derived natural radioprotection compounds:historic development and future perspective

Natural extracts and compounds from marine resources have gained intensive scientific and industry attention for radio-protective activities in the past ten years.However,the marine-derived radioprotectants have been studied against UV-rays,gamma(y)-rays and X-rays for more than 30 years.This review aims to identify key marine-derived extracts/compounds and their modes of action studied for radioprotective activities from 1986 to 2019.A comprehensive survey was conducted to establish the trend in terms of the publications each year and the countries of origin.A total of 40 extracts and 34 natural compounds showing radioprotective activities against UV-rays,gamma(y)-rays and X-rays were identified from a range of marine plants and animals.These extracts and compounds are broadly categorized into polysaccharides,phlorotannins,carotenoids and mycosporine-like amino acids(MAAs).Macroalgae and microalgae were found to be the dominant sources of polysaccharides,phlorotannins and carotenoids.MAAs were mainly identified in algae,sponges,sea cucumber and corals that showed significant UV-absorbing activities.A number of radioprotective mechanisms were shown by these compounds,predominantly free radicals scavenging,inhibition of apoptosis,UV-ray absorption and DNA damage-repair signaling pathways.While these bio-discoveries warrant further investigation and development of radioprotective therapeutics,however,the lack of clinical studies is a major obstacle to be tackled in the future.