Research Paper Volume 15, Issue 5 pp 1358—1370

Ginkgolide A improves the pleiotropic function and reinforces the neuroprotective effects by mesenchymal stem cell-derived exosomes in 6-OHDA-induced cell model of Parkinson’s disease

William Shao-Tsu Chen1,2, , Tzu-Ying Lin3, , Chia-Hua Kuo4, , Dennis Jine-Yuan Hsieh5,6, , Wei-Wen Kuo7, , Shih-Chieh Liao8, , Hui-Chuan Kao9, , Da-Tong Ju10, , Yu-Jung Lin3, *, , Chih-Yang Huang3,11,12,13,14, *, ,

  • 1 Department of Psychiatry, Tzu Chi General Hospital, Hualien 97004, Taiwan
  • 2 School of Medicine Tzu Chi University, Hualien 97004, Taiwan
  • 3 Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
  • 4 Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
  • 5 Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan
  • 6 School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
  • 7 Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
  • 8 Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
  • 9 Department of Public Health, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
  • 10 Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
  • 11 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
  • 12 Department of Biological Science and Technology, Asia University, Taichung, Taiwan
  • 13 Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan
  • 14 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
* Equal contribution

Received: June 14, 2022       Accepted: February 11, 2023       Published: February 20, 2023
How to Cite

Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Parkinson’s disease (PD) is a common disorder attributed to the loss of midbrain dopamine (mDA) neurons and reduced dopamine secretion. Currently, the treatment regimes for PD comprise deep brain stimulations, however, it attenuates the PD progression marginally and does not improve neuronal cell death. We investigated the function of Ginkgolide A (GA) to reinforce Wharton’s Jelly-derived mesenchymal stem cells (WJMSCs) for treating the in vitro model of PD. GA enhanced the self-renewal, proliferation, and cell homing function of WJMSCs as assessed by MTT and transwell co-culture assay with a neuroblastoma cell line. GA pre-treated WJMSCs can restore 6-hydroxydopamine (6-OHDA)-induced cell death in a co-culture assay. Furthermore, exosomes isolated from GA pre-treated WJMSCs significantly rescued 6-OHDA-induced cell death as determined by MTT assay, flow cytometry, and TUNEL assay. Western blotting showed that apoptosis-related proteins were decreased following GA-WJMSCs exosomal treatment which further improved mitochondrial dysfunction. We further demonstrated that exosomes isolated from GA-WJMSCs could restore autophagy using immunofluorescence staining and immunoblotting assay. Finally, we used the alpha-synuclein recombinant protein and found that exosomes derived from GA-WJMSCs led to the reduced aggregation of alpha-synuclein compared to that in control. Our results suggested that GA could be a potential candidate for strengthening stem cell and exosome therapy for PD.


PD: Parkinson’s disease; GA: Ginkgolide A; WJMSCs: Wharton’s Jelly-derived mesenchymal stem cells; mDA: midbrain dopamine; SN: substantia nigra; EVs: extracellular vesicles; 6-OHDA: 6-hydroxydopamine; TH: Tyrosine hydroxylase.