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  3. Neurotoxicity of sanguinarine via inhibiting mitophagy and activating apoptosis in zebrafish and PC12 cells

Neurotoxicity of sanguinarine via inhibiting mitophagy and activating apoptosis in zebrafish and PC12 cells

  • Pestic Biochem Physiol. 2022 Nov:188:105259. doi: 10.1016/j.pestbp.2022.105259.
Xueliang Yang 1,  Lei Li 1,  Yuxin Shi 1,  Xue Wang 1,  Yun Zhang 1,  Meng Jin 1,  Xiqiang Chen 1,  Rongchun Wang 2,  Kechun Liu 3
Affiliations

Affiliations

  • 1 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, 28789 Jingshidong Road, Licheng District, Jinan 250103, Shandong Province, PR China.
  • 2 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, 28789 Jingshidong Road, Licheng District, Jinan 250103, Shandong Province, PR China. Electronic address: [email protected].
  • 3 Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, 28789 Jingshidong Road, Licheng District, Jinan 250103, Shandong Province, PR China. Electronic address: [email protected].
PMID: 36464364 DOI: 10.1016/j.pestbp.2022.105259
Abstract

Sanguinarine, a plant-derived phytoalexin, displays various biological activities, such as insecticidal, antimicrobial, anti-inflammatory, anti-angiogenesis and antitumor effects. But its potential neurotoxicity and the underlying mechanisms has rarely been investigated. Therefore, we aimed to assess the neurotoxicity of sanguinarine using zebrafish model and PC12 cells in this study. The results showed that sanguinarine induced the reduction of the length of dopamine neurons and inhibited the blood vessel in the head area of the zebrafish. Further studies demonstrated that the behavioral phenotype of the larval zebrafish was changed by sanguinarine. In addition, there were more apoptotic cells in the larval zebrafish head area. The mRNA expression levels of β-syn, th, pink1 and parkin, closely related to the nervous function, were changed after sanguinarine treatment. The in vitro studies show that notably increases of ROS and Apoptosis levels in PC12 cells were observed after sanguinarine treatment. Moreover, the protein expression of Caspase3, PARP, Bax, Bcl2, α-Syn, Th, PINK1 and Parkin were also altered by sanguinarine. Our data indicated that the inhibition of Mitophagy, ROS elevation and Apoptosis were involved in the neurotoxicity of sanguinarine. These findings will be useful to understand the toxicity induced by sanguinarine.

Keywords

Apoptosis; Mitophagy; Neurotoxicity; PC12 cell; Sanguinarine; Zebrafish.

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