Coix seed seedlings-derived exosome-like nanovesicles (CSSELNs) have demonstrated significant potential in alleviating ionizing radiation (IR)-induced damage. However, the role of bioactive substances, particularly whether microRNAs (miRNAs) significantly contribute to their radioprotective effects, remains unclear. In this study, we identified miRNAs enriched in CSSELNs by small RNA sequencing, followed by validation of the key miRNAs. It was found that sbi-miR5564a confers protection against IR-induced oxidative stress in THLE-2 cells. Bioinformatics analysis together with cell-based and animal experiments were conducted to explore their potential mechanism. The results indicated that sbi-miR5564a, when delivered through CSSELNs, targeted and downregulated EP300, thereby modulating the JNK/FOXO3a signaling pathway, leading to the restoration of reactive oxygen species to normal levels and protection against IR-induced damage. Notably, a single oral dose of sbi-miR5564a@CSSELNs, which were highly enriched with sbi-miR5564a, exerted highly effective protective effects in vivo, comparable to that achieved by 30-day oral gavage of CSSELNs alone. This study not only clarified the radioprotective effect of sbi-miR5564a but also established CSSELNs as a natural miRNA delivery platform. This advancement promotes the application of plant-derived nanovesicles in radioprotective effects and the development of functional foods.

Radiation technology is widely utilized in the industrial, medical, and military fields. However, high-dose radiation causes significant harm to the human body. Ionizing radiation can alter various epigenetic modifications in animal tissues, thereby influencing phenotypic outcomes, and these effects are transmitted inter- and trans-generationally, making radiation protection particularly important. The development of radioprotective agents represents a major research direction in the field of radiation protection, with natural radioprotective agents offering advantages such as prolonged efficacy and favorable safety profiles. Conventional natural radioprotective agents include polyphenols, polysaccharides, alkaloids, and saponins. In recent years, novel categories have also been identified or developed, such as food-derived exosome-like vesicles, nanotechnology-enabled formulations, and radiation-induced microorganisms. Although some natural radioprotective agents have been successfully applied in the health food industry, their broader development faces several challenges, including incompletely elucidated mechanisms of action, low screening efficiency, high production costs, low bioavailability, and insufficient stability. Future research should address these limitations through three key areas: clarifying the mechanisms underlying radioprotective effects, efficiently screening for functional ingredients, and developing effective delivery systems for active components. Integrated multi-omics approaches, such as transcriptomics, metabolomics and epigenomics, coupled with artificial intelligence are expected to elucidate the mechanisms of action of natural radioprotective agents and enhance the efficiency of screening for functional radioprotective ingredients. Furthermore, biotechnological tools including enzyme engineering, fermentation engineering and synthetic biology enable efficient production of these functional ingredients. Concurrently, natural product-derived formulations, particularly environmentally responsive delivery systems, exhibit improved bioavailability and stability. Additionally, the application scope of natural radioprotective agents across different categories of radiation protection should be expanded. By establishing efficient screening, production, and delivery systems for natural radioprotective agents, their in-depth development and broad application can be promoted.

Microbial food is an important direction of sustainable food development in the future. Microorganisms such as lactic acid bacteria (LAB) are important sources of natural radioprotectors. Moderate environmental stress can induce stress response and improve biological activity of LAB. In the previous study, Lactococcus lactis subsp. lactis IL1403 (L. lactis IL1403) cell-free extract induced by ionizing radiation (IR) of 500 Gy (IR-CFE) presented the stronger radioprotective effect than untreated cell-free extract in mice. To explore the radioprotective active substances of IR-CFE, the key protein was screened by proteomics and its radioprotective effect in vivo was further evaluated. The Kyoto Encyclopedia of Genes and Genomes (KEGG)enrichment showed that two-component systems (TCS) were enhanced to adapt the IR induction. Meanwhile, the protein LlrG belonged to TCS was screened by the protein-protein interaction. Furthermore, the recombinant protein LlrG (rLlrG) could markedly alleviate the ⁶⁰Coγ-induced damage to the hematopoietic system, oxidative stress and inflammation in mice, thereby exerting its radioprotective function. These results suggested LlrG protein not only played an important role in the adaptation of L. lactis IL1403 to IR environment, but also exerted a good radioprotective effect, which could be applied in the development of protein-based radioprotectors.

Plant-derived exosome-like nanovesicles play an important role in regulating the biological functions of organisms. To excavate natural and stable radioprotective nano-agent from coix seed seedlings, the coix seed seedlings-derived exosome-like nanovesicles (CSSELNs) were successfully obtained. CSSELNs with a particle size of 85.85 - 135.7 nm and a surface charge of (-17.1 ± 1.35) mV, were enriched with various functional components including RNAs, proteins and lipids. In addition, CSSELNs demonstrated excellent stability, high cellular uptake efficiency. Cellular experiments demonstrated that CSSELNs effectively alleviated ionizing radiation-induced damage in hepatocytes in vitro. Further in vivo experiments also demonstrated that CSSELNs could exhibit superior radioprotective effects and good safety in mice. Based on these excellent characteristics, CSSELNs have the potential to be developed as a natural and stable radioprotective nano-agent.

Malignant tumor seriously endangers human life and health. Radiotherapy is currently one of the most common treatments for malignant tumor. However, ionizing radiation (IR) can cause radiation resistance of tumor cells and damage normal tissue cells, thereby limiting the clinical application of radiotherapy. Natural polyphenols not only can improve the radiosensitivity of tumor cells, but also can alleviate the negative effects of IR on the body, thus playing an important role in tumor treatment. Dysregulation of non-coding RNA plays an important role in the occurrence and development of many diseases. In recent years, studies have found that the anti-tumor and radiosensitization effects of polyphenols are associated with non-coding RNA regulation. In this context, this paper reviews the anti-tumor and radiosensitization effects of natural polyphenols and their mechanisms, especially from the perspective of non-coding RNA regulation, in order to provide new ideas for the intervention and treatment of tumors and other diseases, as well as the development of food products for special medical purposes.

To explore an ideal alternative approach for radiation protection, this study quantified vitamin C (≥ 2.5%) and total flavonoids (≥ 2%) in Rosa roxbunghii Tratt. juice concentrate. Its antioxidant capacity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation, and hydroxyl radical scavenging assays, and its efficacy in radiation protection was assessed by cell and animal experiments. Results showed that R. roxbunghii Tratt. juice concentrate scavenged all three free radicals and significantly suppressed the reduction in HL-7702 cell viability caused by ionizing radiation. Compared with the radiation model group, the spleen index and superoxide dismutase (SOD) activity in the serum and spleen, the malondialdehyde (MDA) content in the serum and liver, and the glutathione content in the serum, liver and spleen of mice treated with 1.0 g/kg of R. roxbunghii Tratt. juice concentrate for 30 days were significantly alleviated, and it also had a protective effect against liver function damage caused by radiation. This study lay the basis for establishing quality grading standards for R. roxbunghii Tratt. juice concentrate and for its application to functional foods.

Food intake is a major way for the body to obtain materials, energy, and information from the external environment. Food and medicine homology (FMH) substances as food not only contain abundant nutrients, but also carry various bioactive components to promote human health. The special functional factors derived from FMH substances under specific environmental conditions can significantly impact the body’s adaptability. Understanding the complex relationships among environment, FMH substances, and organisms, including the active components of FMH under different environments and their influence on the mechanisms of adaptation to extreme environments, is critical. In this review, the effects of environmental factors on the content and structure of the active components in FMH were comprehensively summarized and discussed, also the effects of FMH on the adaptation of the body to extreme environments. Furthermore, the insights into potential future research directions in the field of FMH and environmental adaptation were provided. This review summarizes the effects of FMH on the body from an environmental perspective and offers new references and insights for the development of FMH.

Chinese yam (Dioscorea opposita Thunb.), as one of the medicinal and edible homologous plants, is rich in various nutrients and functional factors. In this study, Chinese yam fermented by Saccharomyces boulardii was performed to investigate its bioactive components and metabolic profile. And then, the main bioactive components and biological activities of fermented Chinese yam ethanol extract (FCYE) were evaluated. Results showed that there were 49 up-regulated metabolites and 52 down-regulated metabolites in fermented Chinese yam compared to unfermented Chinese yam. Besides, corresponding metabolic pathways analysis initially revealed that the distribution of bioactive substances was concentrated on alcohol-soluble small molecular substances. Ulteriorly, the total polyphenol content and the total flavonoid content in FCYE were significantly increased, and the corresponding antioxidant and immunomodulatory activities in vitro were also significantly enhanced. Our study provided a new reference for the comprehensive utilization of Chinese yam and laid a theoretical foundation for the development and application of natural probiotic-fermented products.

It is well known that exposure to environmental stresses could enhance the adaptability of bacteria and up-regulate the expression of a variety of oxidative stress-related genes and antioxidant enzymes. It is unclear whether the adaptability of microorganisms formed naturally in special environments could transfer to other organisms. The study aimed to evaluate the effects of untreated and ethanol-induced Lactococcus lactis intracellular extracts (U-IE and E-IE) on alcohol metabolism in mice. The positive effects of E-IE on alcohol metabolism in mice were revealed by the enhanced latency of loss of righting reflex (LORR), the reduced duration of LORR, the decrease of blood alcohol concentration, as well as the elevation of alcohol dehydrogenase (ADH) activities in the stomach and liver tissues. Furthermore, the potential benefits of E-IE on the liver were evaluated by biochemical parameters including the activities of serum transaminase, the levels of antioxidant enzymes, and the pathological changes of liver tissue. The present work put forward a new point that appropriate ethanol stress could enhance the intracellular ADH activity of L. lactis, and its intracellular extracts could continue to enhance alcohol metabolism in mice.