Abstract
Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.
Highlights
Radiation source is a kind of physical stress that humans risk in nuclear pollution, space flight and radiation therapy for cancer events [1,2,3]
We mainly investigate its protection against lethal total-body irradiation (TBI) in
These results indicated that the treatment with MASM prevented TBI-induced differential expression out of genes were still differentially expressed in response to
Summary
Radiation source is a kind of physical stress that humans risk in nuclear pollution, space flight and radiation therapy for cancer events [1,2,3]. Several compounds have been reported to offer potential for radiation protection, but most of them are not suitable for clinical application due to their toxicity and poor specificity [4,5,6]. Matrine (molecular formula: C15 H24 N2 O) is an alkaloid found in the herb root of a traditional Chinese medicine, Sophora flavescens Ait [7,8] It has a variety of pharmacological effects and has been wildly used in clinical practice in China for the treatment of viral hepatitis, liver fibrosis, heart arrhythmia and skin inflammation without any obvious side effects [7,8,9,10,11,12,13]. We mainly investigate its protection against lethal TBI in Wistar rats
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