The mechanism of pulmonary fibrosis caused by irradiation remains obscure. Since rosmarinic acid (RA) have anti-oxidant and anti-inflammatory properties, we aimed to evaluate the effect of RA on the X-ray-induced lung injury. Male rats received RA (30, 60, or 120 mg/kg) 7 days before 15 Gy of X-ray irradiation. Here, we showed that RA reduced X-ray-induced the expression of inflammatory related factors, and the level of reactive oxygen species. RA down-regulated the phosphorylation of nuclear factor kappa-B (NF-κB). We found that thoracic tumor patients whose lung regions received radiation showed lower level of microRNA-19b-3p (miR-19b-3p). Furthermore, we provided evidence that miR-19b-3p targets myosin phosphatase target subunit 1 (MYPT1), and RA attenuated RhoA/Rock signaling through upregulating miR-19b-3p, leading to the inhibition of fibrosis. In conclusion, RA may be an effective agent to relieve the pulmonary fibrosis caused by radiotherapy of thoracic tumor.
The parotid glands are damaged by oxidative stress and a series of pathophysiological changes after irradiation. Rosmarinic acid (RA) is a natural antioxidant that provides a radioprotective effect against harmful damage from ionizing radiation. The present study aims to explore the protective effects of RA on radiation-induced parotid gland injury and its underlying mechanism. Sprague-Dawley rats were irradiated with 15 Gy X-ray and treated with different concentrations of RA (30, 60, and 120 mg/kg) or amifostine (AMI, 250 mg/kg). Saliva secretion function, oxidative stress, apoptosis, the inflammatory response, and fibrosis were determined by the measurement of the salivary flow rate, enzyme-linked immunosorbent assay, transferase-mediated DUTP Nick end labeling, Western blot, quantitative real time polymerase chain reaction, and hematoxylin and eosin staining. Here, we show that RA treatment significantly attenuated reactive oxygen species by a direct hindrance effect and the indirect activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nicotinamide adenine dinucleotide phosphate oxidase 4 signaling. Rosmarinic acid not only reduced apoptosis by inhibiting p53/jun N-terminal kinase activation but also reduced parotid gland tissue fibrosis by downregulating inflammatory factor levels. Compared to AMI, RA has the obvious advantages of late efficacy and convenient usage. Moreover, 60 mg/kg is the minimum effective dose of RA. Therefore, RA can potentially be applied as a therapeutic radioprotective agent to treat radiation-induced parotid gland injury in the future.
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