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Citronellol Prevents 6-OHDA-Induced Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Parkinson Disease Model of SH-SY5Y Cells via Modulating ROS-NO, MAPK/ERK, and PI3K/Akt Signaling Pathways

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Abstract

Parkinson disease is a neurodegenerative disorder distinguished by dopaminergic shortage in the striatum and the accumulation of α-synuclein neuronal aggregates in the brains of patients. Since, there is no accurate treatment available for Parkinson disease, researches are designed to alleviate the pathognomonic symptoms such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis. Accordingly, a number of compounds have been reported to inhibit these pathognomonic symptoms. In this study, we have assessed the neuroprotective potential of citronellol against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. The results found that citronellol treatment effectively hindered the cell death caused by 6-OHDA and thereby maintaining the cell viability in SH-SY5Y cells at 50 µg/mL concentration. As expected, the citronellol treatment significantly reduced the 6-OHDA-induced secretion of inflammatory factors (IL-1β, IL-6, and TNF-α), which was obtained through ELISA technique. Similarly, citronellol hindered the 6-OHDA-induced oxidative stress by lowering the intracellular ROS and NO level and MDA leakage along with increased expression of SOD level in SH-SY5Y cells. The JC-1 staining showed that 6-OHDA increased the number of green fluorescent dots with ruptured mitochondrial membrane potential, while citronellol increased the amount of red fluorescent, showing the rescue potential against the 6-OHDA-induced mitochondrial dysfunction. Furthermore, citronellol hampered the 6-OHDA-induced apoptosis via the suppression of Bcl-2/Bax pathway. The western blotting results hypothesized that citronellol rescued SH-SY5Y cells from 6-OHDA-induced neurotoxicity via modulating ROS-NO, MAPK/ERK, and PI3K/Akt signaling pathways. However, further clinical trials are required to verify the anti-Parkinson efficacy.

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All the data presented in the study are included in the article/Supplementary Material.

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Funding

This study was supported by Wenling Social Development Science and Technology Project (NO. 2022S00130, NO.2022S00135), and Taizhou Science and Technology Plan Project (NO. 22YWB131).

Author information

Authors and Affiliations

  1. Department of Neurology, The First People’s Hospital of Wenling, Zhejiang Province, Wenling, 317500, China

    Jiahui Shao, Xuan Liu & Mengjia Lian

  2. Department of Special Inspection Section, The First People’s Hospital of Wenling, No. 333, Chuanan South Road, Chengxi StreetZhejiang Province, Wenling, 317500, China

    Youbing Mao

Authors
  1. Jiahui Shao
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  2. Xuan Liu
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  3. Mengjia Lian
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  4. Youbing Mao
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Contributions

JS: conceptualization performed the experiments, data analysis, and writing-original draft. XL: performed the experiments, data analysis, and writing-original draft. ML: performed the experiments, data analysis, and writing-original draft. YM: conceptualization, supervision, data analysis, and reviewing-original draft. All the authors contributed to the article and approved the submitted version.

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Correspondence to Youbing Mao.

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Shao, J., Liu, X., Lian, M. et al. Citronellol Prevents 6-OHDA-Induced Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Parkinson Disease Model of SH-SY5Y Cells via Modulating ROS-NO, MAPK/ERK, and PI3K/Akt Signaling Pathways. Neurotox Res 40, 2221–2237 (2022). https://doi.org/10.1007/s12640-022-00558-8

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  • DOI: https://doi.org/10.1007/s12640-022-00558-8

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