title: Effects of Ligustrazine on DNA damage and apoptosis induced by irradiation.
abstract: Ligustrazine has been used to treat heart and blood vessel disease in China. In the present study, we investigated the potential action of Ligustrazine as a component of chuanxiong (a Chinese herb) in scavenging hydroxyl radical and superoxide radical as indicated in the ESR spin-trapping measurement. Treatment of Ligustrazine in mice decreased mortality after whole body γ-irradiation. The anti-radiation action of Ligustrazine was studied by measuring DNA damage (Comet assay and γ-H2AX formation) and apoptosis induced by irradiation. It was triggered by altering the level of DNA-PKcs protein, a critical component of DNA double-strand break (DSB) repair pathways in mice after irradiation. Consistently, the phosphorylation of Akt protein, a mediator of survival signaling, was concurrently increased by Ligustrazine treatment. Additionally, the cytokines along with the phosphorylation of the p38 protein which is activated by a variety of environmental stresses and inflammatory cytokines decreased in the Ligustrazine-treated group as compared to irradiation group. Our results suggest that Ligustrazine has radioprotective effect through its capabilities as a powerful antioxidant, in reducing reactive oxygen species (ROS) level induced by irradiation, minimizing DNA damage and apoptosis, and activating survival signal Akt pathways. This study will be of value in the development of novel radioprotective compounds.
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Anhui, Hefei 230032, PR China. Electronic address: hongzheng2013@gmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
authors.forename: Pingkun
authors.initials: P
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Ni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D020552:Comet Assay; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004249:DNA Damage / Q000528:radiation effects*; D004578:Electron Spin Resonance Spectroscopy; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005720:Gamma Rays; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D011719:Pyrazines / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D005609:Free Radicals; D011719:Pyrazines; D017382:Reactive Oxygen Species; D051058:Oncogene Protein v-akt; D048051:p38 Mitogen-Activated Protein Kinases; C017953:tetramethylpyrazine
keywords: Apoptosis; DNA damage; Ligustrazine; Mice; Radioprotection