Amomum subulatum mitigates experimental thoracic radiation-induced lung injury by regulating antioxidant status and inflammatory responses

Radiation-induced lung injury (RILI) is one of the most prominent complications of thoracic radiotherapy for which effective therapy is still lacking. This study investigates the nutraceutical potential of the culinary spice Amomum subulatum in mitigating thoracic radiation-induced pneumonitis (RP) and pulmonary fibrosis (PF). Mouse models of RP and PF were established by whole thorax irradiation at a dose of 25 gray. C57BL/6 mice were administered with 250 mg per kg body weight of methanolic extract of A. subulatum dry fruits (MEAS) for four consecutive weeks and observed for changes in lung tissue antioxidant activities, oxidative stress parameters, and expression of antioxidant, inflammation, and fibrosis-related genes by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR analysis, and histology analysis. MEAS administration reduced radiation-induced oxidative stress by enhancing the expression of Nrf2 and its target genes. Irradiation increased gene expression of inflammatory mediators and lung histology further confirmed the characteristics of RP, which were reduced by MEAS treatment. Immunohistochemistry analysis revealed the potential of MEAS in reducing the radiation-induced elevation of cyclooxygenase 2 expression in the lungs. The late sequel of RILI was manifested as PF, characterized by the elevated expression of pro-fibrotic genes and increased collagen content. However, MEAS administration markedly reduced radiation-induced fibrotic changes in the lungs. These effects might be attributed to the synergistic effect of bioactive polyphenols in MEAS with antioxidant, anti-inflammatory, and anti-fibrotic efficacies. Taken together, this study demonstrates the potential of MEAS in mitigating RILI, suggesting the possible nutraceutical application of A. subulatum against radiation toxicities.