Botanical Drug Puerarin Attenuates 6-Hydroxydopamine (6-OHDA)-Induced Neurotoxicity via Upregulating Mitochondrial Enzyme Arginase-2

Jia Zhao, Yuanyuan Cheng, Chuanbin Yang, Sam Lau, Lixing Lao, Bo Shuai, Jing Cai, Jianhui Rong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

23 Citations (Scopus)


Inhibition of nitric oxide synthases (NOSs) shows promise to halt the progression of neurodegenerative diseases. The present study was designed to explore whether botanical isoflavone puerarin could attenuate nitric oxide (NO)-mediated neurotoxicity via modulating the enzymes in the L-arginine–NO pathway. Neurotoxin 6-hydroxydopamine (6-OHDA) is well known to induce neurodegeneration via a NO-dependent mechanism. We first validated that puerarin protected rat dopamingeric PC12 cells against 6-OHDA-induced neurotoxicity in a concentration-dependent manner. We subsequently profiled the cellular responses to puerarin by a proteomic response fingerprinting approach. A total of 16 protein spots with >1.5-fold change of intensity were selected and identified by mass spectrometry. As one of puerarin-upregulated proteins, mitochondrial arginase-2 hydrolyzes L-arginine to L-ornithine, thereby competing with neuronal NOS for substrate L-arginine in mitochondria. Thus, we hypothesize that puerain may attenuate nitric oxide (NO)-mediated mitochondrial injury via increasing arginase-2 expression. Western blot and reverse transcription polymerase chain reaction (RT-PCR) analyses confirmed that puerarin increased arginase-2 expression in a concentration- and time-dependent manner. Accordingly, puerarin suppressed 6-OHDA-induced NO production and neurotoxicity in PC12 cells and primary rat midbrain neurons. Arginase inhibitor BEC diminished the effect of puerarin on 6-OHDA-induced NO production and neurotoxicity. The activation of arginase-2 by puerarin represents an endogenous mechanism for specific control of NO-mediated mitochondrial damage. Thus, puerarin is a useful lead for suppressing NO-mediated neurotoxicity in neurodegenerative diseases. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)2200-2211
Number of pages12
JournalMolecular Neurobiology
Issue number4
Publication statusPublished - 1 May 2016

Scopus Subject Areas

  • Neurology
  • Cellular and Molecular Neuroscience

User-Defined Keywords

  • Arginase-2
  • Neuroprotection
  • Nitric oxide
  • Parkinson’s disease
  • Puerarin


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