Neurochemical Research

, Volume 42, Issue 4, pp 1130–1140 | Cite as

Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway

  • Xi Wang
  • Xiaocheng Lu
  • Ronglan Zhu
  • Kaixin Zhang
  • Shuai Li
  • Zhongjun Chen
  • Lixin Li
Original Paper


Betulinic acid (BA), a pentacyclic triterpene of natural origin, has been demonstrated to have varied biologic activities including anti-viral, anti-inflammatory, and anti-malarial effects; it has also been found to induce apoptosis in many types of cancer. However, little is known about the effect of BA on normal cells. In this study, the effects of BA on normal neuronal cell apoptosis and the mechanisms involved were studied using differentiated PC12 cells as a model. Treatment with 50 μM BA for 24 h apparently induced PC12 cell apoptosis. In the early stage of apoptosis, the level of intracellular reactive oxygen species (ROS) increased. Afterwards, the loss of the mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3 occurred. Treatment with antioxidants could significantly reduce BA-induced PC12 cell apoptosis. In conclusion, we report for the first time that BA induced the mitochondrial apoptotic pathway in differentiated PC12 cells through ROS.


BA PC12 cells Apoptosis Mitochondrial ROS 



This study was supported by grants from the National Natural Science Foundation of China (No. 81171147), “Xingwei Project” Key Personal Medical Research Foundation of Health Department of Jiangsu Province (No. RC201156), “Six Categories of Key Person” Research Foundation of Jiangsu Province (No. 069), and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. JX10231801).

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflicts of interests.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Xi Wang
    • 1
  • Xiaocheng Lu
    • 2
  • Ronglan Zhu
    • 3
  • Kaixin Zhang
    • 1
    • 4
  • Shuai Li
    • 1
  • Zhongjun Chen
    • 1
    • 5
  • Lixin Li
    • 1
  1. 1.Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of NeurosurgeryThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  3. 3.Department of NeurosurgeryJiangxi Provincial People’s HospitalNanchangChina
  4. 4.Department of NeurosurgeryHuangshan City People’s HospitalHuangshanChina
  5. 5.Department of NeurosurgeryThe Second People’s Hospital of Huai’anHuai’anChina

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