Human Urine Extract Cell Differentiation Agent 2 Protects PC12 Cells from Serum Deprivation-Induced Apoptosis Accompanied with Priming of Extracellular Signal-Regulated Kinase Activation and Differentiation Induction

Chih jung Yao, Shuang en Chuang, Ya yu Yang, Gi ming Lai

Research output: Contribution to journalArticle


Objective: To investigate the potential neuroprotective effect of human urine extract cell differentiation agent 2 (CDA-2) by the model of serum deprivation-induced apoptosis of PC12 cells and study the underlying molecular mechanisms. Methods: Apoptosis of PC12 cells was induced by serum deprivation. CDA-2 at doses of 0.5–4 mg/mL was used to treat the serum-deprived PC12 cells. The cellular viability was measured by sulforhodamine B binding assay and the cell apoptosis was determined by flow cytometer. Western blot was used to analyze the expression of differentiation markers and activity of extracellular signal-regulated kinase (ERK). The cellular morphology was examined under an inverted microscope. Results: CDA-2 inhibited apoptotic cell death of serum-deprived PC12 cells in a dose-dependent manner. Expression of low- and mid-sized neurofilaments was observed in serum-deprived PC12 cells treated with CDA-2 or nerve growth factor (NGF). However, CDA-2 did not induce proliferation of these cells like NGF. The morphology of CDA-2 treated cells was changed from rounded to neuron-like flat polygonal shape in contrast to the extensive neurite outgrowth induced by NGF. CDA-2 transiently induced the phosphorylation of ERK in serum deprived-PC12 cells and the expression of neurofilaments induced by CDA-2 was attenuated by mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059. Conclusions: Human urine extract CDA-2 showed a potential neuroprotective activity which may correlate with ERK activation and differentiation induction.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalChinese Journal of Integrative Medicine
Publication statusAccepted/In press - Feb 17 2018



  • anti-apoptosis
  • cell differentiation agent 2
  • Chinese medicine
  • differentiation
  • extracellular signal-regulated kinase
  • human urine extract
  • neuroprotection

ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Pharmacology (medical)

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