Amomum subulatum mitigates total body irradiation-induced oxidative stress and its associated inflammatory response by enhancing the antioxidant status and regulating the pro-inflammatory cytokines

Free radical-induced oxidative damage and associated inflammatory responses play a crucial role in cancer radiotherapy (RT) mediated normal tissue toxicities. Supplementation of antioxidants or inflammation modulators may alleviate RT toxicity, thereby improving clinical outcomes. Amomum subulatum is a dietary spice rich in biologically active phytochemicals. The present study investigates radiation dose-modifying factor (DMF) and radioprotective efficacy of methanolic extract of Amomum subulatum dry fruits (MEAS) in mice exposed to different doses of total body irradiation (TBI). Administration of MEAS resulted in a DMF of 1.25 Gy, ascertaining its radioprotective efficacy. MEAS reversed X-ray-induced redox imbalance by enhancing antioxidant defense mechanisms. MEAS prevented TBI-induced hematopoietic damages by significantly (P<.01) enhancing bone marrow cellularity, total white blood cell count, and hemoglobin level. MEAS prevented p53-mediated apoptotic death of intestinal cells and increased the expression of cytoprotective genes Nrf2 (nuclear factor-erythroid factor 2-related factor 2) and HO-1 (heme oxygenase-1). Expression of apoptosis regulating genes revealed that MEAS reduced radiation-induced apoptotic death of intestinal cells. Treatment with MEAS also reduced inflammatory responses via reversing TBI-induced elevation in serum pro-inflammatory cytokine (TNF-alpha, IL-1 beta, IL-6) levels. Tissue histopathology further confirmed the protective effect of MEAS against TBI-induced inflammatory responses, suggesting the potential of MEAS in modulating inflammation. These effects might perhaps be attributed to the synergistic effect of biologically active polyphenols with antioxidant, anti-inflammatory, and Nrf2 activating potential in MEAS. Our findings demonstrated the radioprotective efficacy of MEAS, suggesting the possible nutraceutical application of Amomum subulatum in modulating oxidative stress and inflammation. (C) 2022 Elsevier Inc. All rights reserved.