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Chrysoeriol mediates mitochondrial protection via PI3K/Akt pathway in MPP+ treated SH-SY5Y cells.
Neurosci Lett. 2020 01 01; 714:134545.NL

Abstract

Chrysoeriol is a plant flavone extracted from the roots and leaves of the genus Phyllanthus. Although many biological properties of chrysoeriol have been reported, such as its antioxidant and anti-inflammatory activities, the effects of chrysoeriol on the cellular models of Parkinson's disease (PD) have not yet been elucidated. In the present study, we aimed to investigate whether chrysoeriol prevents neurotoxicity induced by 1-methyl-4-phenylpyridinium iodide (MPP+) in SH-SY5Y cells, a typical in vitro PD model. The cell viability was measured by MTT assay. The morphological changes of apoptotic cell nuclei were observed by Hoechst 33,342 staining. The expression of Bax, Bcl-2 and Caspase-3 were detected by western blot analysis. The mitochondria location in the cells was observed by Mitotracker staining. Mitochondrial membrane potential was evaluated by the JC-10 assay. Treatment with MPP+ significantly caused a decrease in the viability of cells and an increase in apoptosis, as evidenced by the upregulation of apoptotic cells, caspase-3 activity and antiapoptotic ratio. These effects were all reversed by pretreatment with chrysoeriol in SH-SY5Y cells. Moreover, pretreatment with chrysoeriol markedly mitigated the MPP+-caused increases in the levels of the prosurvial signaling proteins, phosphorylated Akt and phosphorylated mTOR. The presence of a specific PI3K inhibitor, wortmannin, particularly abolished the chrysoeriol-induced activation of Akt phosphorylation and prevented the chrysoeriol-induced survival effect. These results indicate that the neuroprotective effect of chrysoeriol against MPP+ treatment requires the activation of PI3K/Akt pathway. Ultimately, chrysoeriol could be a promising therapeutic agent for the further experiment on the treatment of PD.

Authors+Show Affiliations

Anatomy and Structural Biology Graduate Program, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: llim.tanapol@gmail.com.Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.Department of Anatomy and Center for Neuroscience, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand. Electronic address: sukumal.cho@mahidol.ac.th.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31622648

Citation

Limboonreung, Tanapol, et al. "Chrysoeriol Mediates Mitochondrial Protection Via PI3K/Akt Pathway in MPP+ Treated SH-SY5Y Cells." Neuroscience Letters, vol. 714, 2020, p. 134545.
Limboonreung T, Tuchinda P, Chongthammakun S. Chrysoeriol mediates mitochondrial protection via PI3K/Akt pathway in MPP+ treated SH-SY5Y cells. Neurosci Lett. 2020;714:134545.
Limboonreung, T., Tuchinda, P., & Chongthammakun, S. (2020). Chrysoeriol mediates mitochondrial protection via PI3K/Akt pathway in MPP+ treated SH-SY5Y cells. Neuroscience Letters, 714, 134545. https://doi.org/10.1016/j.neulet.2019.134545
Limboonreung T, Tuchinda P, Chongthammakun S. Chrysoeriol Mediates Mitochondrial Protection Via PI3K/Akt Pathway in MPP+ Treated SH-SY5Y Cells. Neurosci Lett. 2020 01 1;714:134545. PubMed PMID: 31622648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chrysoeriol mediates mitochondrial protection via PI3K/Akt pathway in MPP+ treated SH-SY5Y cells. AU - Limboonreung,Tanapol, AU - Tuchinda,Patoomratana, AU - Chongthammakun,Sukumal, Y1 - 2019/10/14/ PY - 2019/02/01/received PY - 2019/08/09/revised PY - 2019/10/09/accepted PY - 2019/10/18/pubmed PY - 2019/10/18/medline PY - 2019/10/18/entrez KW - Chrysoeriol KW - MPP(+) KW - Neurodegeneration KW - PI3K KW - Parkinson’s disease KW - Wortmannin SP - 134545 EP - 134545 JF - Neuroscience letters JO - Neurosci Lett VL - 714 N2 - Chrysoeriol is a plant flavone extracted from the roots and leaves of the genus Phyllanthus. Although many biological properties of chrysoeriol have been reported, such as its antioxidant and anti-inflammatory activities, the effects of chrysoeriol on the cellular models of Parkinson's disease (PD) have not yet been elucidated. In the present study, we aimed to investigate whether chrysoeriol prevents neurotoxicity induced by 1-methyl-4-phenylpyridinium iodide (MPP+) in SH-SY5Y cells, a typical in vitro PD model. The cell viability was measured by MTT assay. The morphological changes of apoptotic cell nuclei were observed by Hoechst 33,342 staining. The expression of Bax, Bcl-2 and Caspase-3 were detected by western blot analysis. The mitochondria location in the cells was observed by Mitotracker staining. Mitochondrial membrane potential was evaluated by the JC-10 assay. Treatment with MPP+ significantly caused a decrease in the viability of cells and an increase in apoptosis, as evidenced by the upregulation of apoptotic cells, caspase-3 activity and antiapoptotic ratio. These effects were all reversed by pretreatment with chrysoeriol in SH-SY5Y cells. Moreover, pretreatment with chrysoeriol markedly mitigated the MPP+-caused increases in the levels of the prosurvial signaling proteins, phosphorylated Akt and phosphorylated mTOR. The presence of a specific PI3K inhibitor, wortmannin, particularly abolished the chrysoeriol-induced activation of Akt phosphorylation and prevented the chrysoeriol-induced survival effect. These results indicate that the neuroprotective effect of chrysoeriol against MPP+ treatment requires the activation of PI3K/Akt pathway. Ultimately, chrysoeriol could be a promising therapeutic agent for the further experiment on the treatment of PD. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/31622648/Chrysoeriol_mediates_mitochondrial_protection_via_PI3K/Akt_pathway_in_MPP+_treated_SH_SY5Y_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(19)30648-2 DB - PRIME DP - Unbound Medicine ER -