Li Jianzhong, Xu Jing, Lu Yiming, Qiu Lei, Xu Weiheng, Lu Bin, Hu Zhenlin, Chu Zhiyong, Chai Yifeng, Zhang Junping
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Department of Pharmacy, East Hospital, Dongji University, Shanghai 200085, China.
Molecules. 2016 May 17;21(5):649. doi: 10.3390/molecules21050649.
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.
苦参碱是从苦参中提取的一种生物碱，具有多种生物活性，如抗炎、抗肿瘤、抗纤维化和免疫抑制特性。在我们之前的研究中，合成了苦参碱衍生物MASM，它对肝纤维化表现出强大的抑制活性。在本研究中，我们主要探讨了其对大鼠致死性全身照射（TBI）的保护作用。给予MASM可减轻辐射病特征，并提高致死性TBI前后大鼠的30天存活率。超微结构观察表明，用MASM预处理大鼠可显著减轻TBI诱导的受照大鼠不同器官的形态学变化。基因表达谱显示，用MASM预处理对TBI引起的基因表达变化有显著影响。用MASM预处理可阻止TBI诱导的1445个差异表达基因中53%（765个基因）的差异表达。通路富集分析表明，这些基因主要涉及总共21条通路，如代谢通路、癌症通路和丝裂原活化蛋白激酶（MAPK）通路。我们的数据表明，用MASM预处理大鼠可调节TBI诱导的这些通路，这表明用MASM预处理可能主要或部分通过调节这些通路（如多种MAPK通路）对致死性TBI提供保护作用。因此，MASM有潜力用作一种有效的治疗或辐射防护剂，以尽量减少辐射损伤，并与放疗联合使用以提高癌症治疗的疗效。
