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Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System In Vivo

Title
Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System In Vivo
Authors
Leem, EunjuOh, Yong-SeokShin, Won-HoJin, Byung KwanJeong, Jae YeongShin, MinsangKim, Dong WoonJang, Jin-HyeokKim, Hyung-JunHa, Chang ManJung, Un JuMoon, Gyeong JoonKim, Sang Ryong
DGIST Authors
Leem, Eunju; Oh, Yong-Seok; Shin, Won-Ho; Jin, Byung Kwan; Jeong, Jae Yeong; Shin, Minsang; Kim, Dong Woon; Jang, Jin-Hyeok; Kim, Hyung-Jun; Ha, Chang Man; Jung, Un Ju; Moon, Gyeong Joon; Kim, Sang Ryong
Issue Date
2019-03
Citation
Journal of Medicinal Food, 22(3), 277-285
Type
Article
Article Type
Article
Author Keywords
microglianeurodegenerationnigrostriatal dopaminergic systemprothrombin kringle-2silibinin
Keywords
PARKINSONS-DISEASEOXIDATIVE STRESSMOUSE MODELNEURONSPROTECTSNEUROINFLAMMATIONTRANSDUCTIONINDUCTIONDEATH
ISSN
1096-620x
Abstract
Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy. © 2019, Mary Ann Liebert, Inc.
URI
http://hdl.handle.net/20.500.11750/9713
DOI
10.1089/jmf.2018.4266
Publisher
한국식품영양과학회
Related Researcher
  • Author Oh, Yong-Seok Molecular Psychiatry Lab
  • Research Interests Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
Files:
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Collection:
Department of Brain and Cognitive SciencesMolecular Psychiatry Lab1. Journal Articles
Department of Brain and Cognitive SciencesBrain and Cognitive Sciences Research Center1. Journal Articles


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