Analyzing the effects of silibinin against prothrombin kringle-2-induced neurodegeneration

In this study, researchers from different universities in South Korea demonstrated how silibinin, a flavonoid found in milk thistle, can be used for Parkinson’s disease therapy.  The results of their study were published in the Journal of Medicinal Food.

• Both Parkinson’s disease and Alzheimer’s disease exhibit common features of neurodegenerative diseases and are caused by numerous factors.
• One common feature of both diseases is neurotoxic inflammation caused by activated microglia. The regulation of microglial activation is a potential mechanism for preserving neurons in the brains of patients with Alzheimer’s or Parkinson’s.
• In a previous study, researchers reported that the upregulation of prothrombin kringle-2 (pKr-2), a prothrombin domain that is cleaved and generated by active thrombin, can induce neurotoxic microglial activation, which leads to nigral dopaminergic neuronal death.
• To determine the effect of silibinin, they treated mice substantia nigra with the flavonoid and pKr-2.
• They found that silibinin can suppress the production of inducible nitric oxide synthase (iNOS) and neurotoxic inflammatory cytokines like interleukin-1B and tumor necrosis factor-a (TNF-a). This inhibition happens via the downregulation of the extracellular signal-regulated kinase signaling pathway.
• The researchers also performed immunohistochemical staining, measured dopamine and metabolite levels, and conducted open-field behavioral tests to evaluate silibinin activity.
• They reported that silibinin treatment protected the nigrostriatal dopaminergic system from pKr-2-triggered neurotoxic inflammation in vivo.

Based on these results, the researchers concluded that silibinin is a beneficial natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity. They believe that it can be used to protect the nigrostriatal dopaminergic pathway and treat Parkinson’s disease.

Journal Reference:

Leem E, Oh YS, Shin W-H, Jin BK, Jeong JY, Shin M, Kim DW, Jang JH, Kim HJ, Ha CM, Jung UJ, Moon GJ, Kim SR. EFFECTS OF SILIBININ AGAINST PROTHROMBIN KRINGLE-2-INDUCED NEUROTOXICITY IN THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN VIVO. Journal of Medicinal Food. 15 March 2019;22(3):277–285. DOI: 10.1089/jmf.2018.4266