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Radiation-induced intestinal injury is a common complication of radiotherapy for abdominal and pelvic malignancies. Due to its rapid proliferation, the small intestine is particularly sensitive to radiation, making it a critical factor limiting treatment. Ferulic acid (FA), a derivative of cinnamic acid, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we established a mouse model of radiation-induced intestinal injury using a dose of 11 Gy at a rate of 96.62 cGy/min. Our findings indicate that FA's protective effects against radiation-induced intestinal injury may be mediated through the parkinsonism-associated deglycase (DJ-1) nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homolog 1 (Sirt1) nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) NOD-like receptor family, pyrin domain containing 3 (NLRP3). FA was found to mitigate changes in oxidative stress indices and inflammatory factors induced by radiation, as well as to attenuate radiation-induced pathological alterations in the small intestine. Furthermore, FA enhanced the expression of DJ-1 and Nrf2 at both the transcriptional and protein levels, inhibited NLRP3 protein fluorescence intensity, and reduced the expression of NLRP3, interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). Additionally, FA suppressed the transcription and translation of NF-κB, NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), IL-18, and IL-1β by upregulating Sirt1, thereby alleviating radiation-induced inflammatory injury in the small intestine. Thus, FA holds promise as an effective therapeutic agent for ameliorating radiation-induced intestinal injury. [ABSTRACT FROM AUTHOR] more...

The disruption of hematopoietic and immune functions is a significant consequence of the long-term effects of radiation exposure. This study investigated the potential mechanisms by which ferulic acid (FA) acts as a radioprotective agent in mitigating radiation-induced immune damage. C57BL/6J mice were exposed to a dose of 6.0 Gy of 60Co γ irradiation. FA was administered at doses of 25, 50, and 100 mg/kg/d for 7 days before and 30 days following irradiation. We evaluated changes in peripheral blood cells, T and B lymphocytes, natural killer cells in the spleen, and hematopoietic stem/progenitor cells in the bone marrow (BM). Whole-genome transcriptome sequencing of BM was performed to explore potential mechanisms. FA administration resulted in a significant reduction in malonaldehyde levels (p < 0.0001), an increase in catalase and beta-nicotinamide adenine dinucleotide levels in serum (p < 0.05), and enhanced multipotent progenitors (p < 0.01) and common lymphoid progenitors (p < 0.05) in the BM. Additionally, there was an elevation in white blood cell levels, red blood cell levels, and hemoglobin levels in peripheral blood (p < 0.01). Transcriptome analysis indicated that FA reversed the radiation-induced expression of genes related to immunity and inflammation. Enzyme-linked immunosorbent assay experiments further demonstrated that FA reduced interleukin-6 levels in the BM and decreased JAK1, JAK2, and STAT3 protein content (p < 0.01). In conclusion, FA might mitigate hematopoietic and immune damage by modulating the JAK/STAT signaling pathway. [ABSTRACT FROM AUTHOR] more...

After radiation therapy of brain tumors, radiation-induced cognitive impairment is a common and severe complication. Neuroinflammation mediated by microglia is a critical event that accelerates cognitive or functional decline. Ferulic acid (FA), a phenolic plant component, possesses multiple pharmacological effects, such as anti-inflammatory and anti-radiation. The current research attempts to ascertain the protection of FA on radiation-induced neuroinflammation and the mechanism of this effect. C57BL/6 mice were irradiated with 60Co γ-ray to establish a brain injury model. The Morris water maze experiment was used to observe the effects of FA on the spatial learning and memory impairment of irradiated mice. The pathological changes of hippocampal tissue were observed by HE staining. Besides, microglia BV-2 cell lines were used to study the anti-neuroinflammatory impacts of FA on radiation-induced microglial activation and further elucidate the potential mechanisms influencing FA-mediated neuroprotective properties. The cell morphological changes were observed using an optical microscope. The cytotoxicity of FA and radiation to BV-2 cells was determined using the CCK-8 assay. Additionally, Western blot and quantitative real-time PCR detected the expression and transcription of NLRP3 inflammasome and pro-inflammatory cytokines in hippocampus and BV-2 cells. FA could enhance learning and memory capacity and ameliorate pathological changes in the hippocampal tissues of irradiated mice. The cell radiation injury model was established by 8 Gy 60Co γ-ray, and the concentration of subsequent administration was determined to be 2.5, 5, and 10 μmol/L. Furthermore, FA could suppress the transcription and expression of NLRP3 in hippocampal tissue and microglia, and also the increased secretion of pro-inflammatory factors. This study established that FA targeting the NLRP3 inflammasome has a neuroprotective effect against radiation-induced nerve damage, implying that FA might have some potential in the treatment of radiation-induced cognitive impairment. [ABSTRACT FROM AUTHOR] more...