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

Eunju Leem, Yong Seok Oh, Won Ho Shin, Byung Kwan Jin, Jae Yeong Jeong, Minsang Shin, Dong Woon Kim, Jin Hyeok Jang, Hyung Jun Kim, Chang Man Ha, Un Ju Jung, Gyeong Joon Moon, Sang Ryong Kim

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)277-285
Number of pages9
JournalJournal of Medicinal Food
Volume22
Issue number3
DOIs
StatePublished - 1 Mar 2019

Bibliographical note

Publisher Copyright:
© 2019, Mary Ann Liebert, Inc.

Keywords

  • microglia
  • neurodegeneration
  • nigrostriatal dopaminergic system
  • prothrombin kringle-2 silibinin

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