33 引文 斯高帕斯(Scopus)

摘要

Lovastatin, a secondary metabolite isolated from Monascus-fermented red rice mold, has neuroprotective activity and permeates the blood-brain barrier. The aim of this study was to enhance the activity of lovastatin for potential use as a treatment for neuronal degeneration in Parkinson's disease. Six lovastatin-derived compounds were semisynthesized and screened for neurocytoprotective activity against 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma PC12 cells. Four compounds, designated as 3a, 3d, 3e, and 3f, significantly enhanced cell viability. In particular, compound 3f showed excellent neurocytoprotective activity (97.0 ± 2.7%). Annexin V-FITC and propidium iodide double staining and 4′,6-diamidino-2-phenylindole staining indicated that compound 3f reduced 6-OHDA-induced apoptosis in PC12 cells. Compound 3f also reduced caspase-3, -8, and -9 activities, and intracellular calcium concentrations elevated by 6-OHDA in a concentration-dependent manner, without inhibiting reactive oxygen species generation. JC-1 staining indicated that compound 3f also stabilized mitochondrial membrane potential. Thus, compound 3f may be used as a neurocytoprotective agent. Future studies should investigate its potential application as a treatment for Parkinson's disease.
原文英語
頁(從 - 到)716-724
頁數9
期刊ACS Chemical Neuroscience
6
發行號5
DOIs
出版狀態已發佈 - 5月 20 2015

ASJC Scopus subject areas

  • 認知神經科學
  • 生物化學
  • 生理學
  • 細胞生物學

指紋

深入研究「Neurocytoprotective effects of aliphatic hydroxamates from lovastatin, a secondary metabolite from monascus -fermented red mold rice, in 6-hydroxydopamine (6-OHDA)-Treated Nerve Growth Factor (NGF)-Differentiated PC12 Cells」主題。共同形成了獨特的指紋。

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