title: MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats.
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.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. lijianzhong1234@hotmail.com.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. xujing0601103@live.cn.|Department of Pharmacy, East Hospital, Dongji University, Shanghai 200085, China. xujing0601103@live.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. bluesluyi@163.com.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. qlcong021@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. xuweiheng7114@163.com.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. binlu@smmu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. zhenlinhu@hotmail.com.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: The Naval Medical Research Institute, Shanghai 200433, China. zhiyongchu@tom.com.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Chu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. yfchai@smmu.edu.cn.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Chai
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. jpzhang08@hotmail.com.
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D011807:Quinolizines / Q000008:administration & dosage* / Q000737:chemistry; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D029909:Sophora / Q000737:chemistry*; D014916:Whole-Body Irradiation; D000093842:Matrines
chemical_list: D000470:Alkaloids; D010936:Plant Extracts; D011807:Quinolizines; D011837:Radiation-Protective Agents; D020929:Mitogen-Activated Protein Kinase Kinases; D000093842:Matrines
keywords: MAPK pathways; MASM; gene expression; radiation lethality; radioprotection; total-body irradiation