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Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway

  • Authors:
    • Rixin Luo
    • Lihong Zhu
    • Zhaohao Zeng
    • Ruiyi Zhou
    • Jiawei Zhang
    • Shu Xiao
    • Wei Bi
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 597
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    Published online on: April 9, 2021
       https://doi.org/10.3892/etm.2021.10029
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Abstract

Activated microglia are a source of superoxide which often increases oxidative stress in the brain microenvironment, increase production of reactive oxygen species (ROS) and directly or indirectly lead to dopaminergic neuronal death in the substantia nigra. Thus superoxide contributes to the pathogenesis of Parkinson's disease (PD). Evidence suggests that mitochondria are the main source of ROS, which cause oxidative stress in cells. Levels of ROS are thus associated with the function of the mitochondrial complex. Therefore, protecting the mitochondrial function of microglia is important for the treatment of PD. Dl‑butylphthalide (NBP), a compound isolated from Chinese celery seeds, has been approved by the China Food and Drug Administration for the treatment of acute ischemic stroke. Recently, NBP demonstrated therapeutic potential for PD. However, the mechanism underlying its neuroprotective effect remains unclear. The present study aimed to investigate the effect of NBP on rotenone‑induced oxidative stress in microglia and its underlying mechanisms. The results demonstrated that NBP treatment significantly increased mitochondrial membrane potential and decreased ROS level in rotenone‑induced microglia. Western blot analysis showed that NBP treatment promoted entry of nuclear respiratory factor‑2 (Nrf2) into the nucleus, increased heme oxygenase‑1 (HO‑1) expression and decreased the level of the Nrf2 inhibitory protein, Kelch‑like ECH‑associated protein 1. Overall, the findings indicated that NBP inhibited rotenone‑induced microglial oxidative stress via the Keap1/Nrf2/HO‑1 pathway, suggesting that NBP may serve as a novel agent for the treatment of PD.
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Copy and paste a formatted citation
Spandidos Publications style
Luo R, Zhu L, Zeng Z, Zhou R, Zhang J, Xiao S and Bi W: Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway. Exp Ther Med 21: 597, 2021.
APA
Luo, R., Zhu, L., Zeng, Z., Zhou, R., Zhang, J., Xiao, S., & Bi, W. (2021). Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway. Experimental and Therapeutic Medicine, 21, 597. https://doi.org/10.3892/etm.2021.10029
MLA
Luo, R., Zhu, L., Zeng, Z., Zhou, R., Zhang, J., Xiao, S., Bi, W."Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway". Experimental and Therapeutic Medicine 21.6 (2021): 597.
Chicago
Luo, R., Zhu, L., Zeng, Z., Zhou, R., Zhang, J., Xiao, S., Bi, W."Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway". Experimental and Therapeutic Medicine 21, no. 6 (2021): 597. https://doi.org/10.3892/etm.2021.10029
Copy and paste a formatted citation
x
Spandidos Publications style
Luo R, Zhu L, Zeng Z, Zhou R, Zhang J, Xiao S and Bi W: Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway. Exp Ther Med 21: 597, 2021.
APA
Luo, R., Zhu, L., Zeng, Z., Zhou, R., Zhang, J., Xiao, S., & Bi, W. (2021). Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway. Experimental and Therapeutic Medicine, 21, 597. https://doi.org/10.3892/etm.2021.10029
MLA
Luo, R., Zhu, L., Zeng, Z., Zhou, R., Zhang, J., Xiao, S., Bi, W."Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway". Experimental and Therapeutic Medicine 21.6 (2021): 597.
Chicago
Luo, R., Zhu, L., Zeng, Z., Zhou, R., Zhang, J., Xiao, S., Bi, W."Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway". Experimental and Therapeutic Medicine 21, no. 6 (2021): 597. https://doi.org/10.3892/etm.2021.10029
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