2. Academic Validation
  3. Effect of Vasicinone against Paraquat-Induced MAPK/p53-Mediated Apoptosis via the IGF-1R/PI3K/AKT Pathway in a Parkinson's Disease-Associated SH-SY5Y Cell Model

Effect of Vasicinone against Paraquat-Induced MAPK/p53-Mediated Apoptosis via the IGF-1R/PI3K/AKT Pathway in a Parkinson's Disease-Associated SH-SY5Y Cell Model

  • Nutrients. 2019 Jul 19;11(7):1655. doi: 10.3390/nu11071655.
Da-Tong Ju 1,  Kalaiselvi Sivalingam 2,  Wei-Wen Kuo 3,  Tsung-Jung Ho 4,  Ruey-Lin Chang 5,  Li-Chin Chung 6,  Cecilia Hsuan Day 7,  Vijaya Padma Viswanadha 8,  Po-Hsiang Liao 9 10,  Chih-Yang Huang 11 12 13 14 15
Affiliations

Affiliations

  • 1 Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
  • 2 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
  • 3 Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan.
  • 4 Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan.
  • 5 School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
  • 6 Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan 717, Taiwan.
  • 7 Department of Nursing, MeiHo University, Pingtung 912, Taiwan.
  • 8 Department of Biotechnology, Bharathiar University, Tamilnadu 641046, India.
  • 9 Cardiovascular and Mitochondria related diseases research center, Hualien Tzu Chi Hospital, Hualien 970, Taiwan.
  • 10 Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan.
  • 11 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. [email protected].
  • 12 Cardiovascular and Mitochondria related diseases research center, Hualien Tzu Chi Hospital, Hualien 970, Taiwan. [email protected].
  • 13 Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan. [email protected].
  • 14 Graduate Institute of Biomedicine, China Medical University and Hospital, Taichung 404, Taiwan. [email protected].
  • 15 Department of Biotechnology, Asia University, Taichung 413, Taiwan. [email protected].
PMID: 31331066 DOI: 10.3390/nu11071655
Abstract

Vasicinone is a quinazoline alkaloid isolated from the Adhatoda vasica plant. In this study, we explored the neuroprotective effect and underlying molecular mechanism of vasicinone against paraquat-induced cellular Apoptosis in SH-SY5Y cells. Vasicinone reduced the paraquat-induced loss of cell viability, rescued terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic nuclei, and suppressed generation of Reactive Oxygen Species (ROS) in a dose-dependent manner. Western blotting analysis revealed that vasicinone increased the phosphorylation of IGF1R/PI3K/Akt cell survival signaling molecules and downregulated the paraquat-induced, mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK)-mediated apoptotic pathways compared to that observed in cells not treated with vasicinone. This protection depended critically on the activation of IGF1R, and the silencing of IGF1R by siRNA completely abrogated the protective effect of vasicinone in SH-SY5Y cells. Our findings indicated that vasicinone is a potential candidate for the treatment of Parkinson's disease and possibly other oxidative stress-related neurodegenerative disorders.

Keywords

apoptosis; neuroprotection; paraquat; parkinson’s disease; reactive oxygen species; vasicinone.

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