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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neuropharmacology
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1432969
This article is part of the Research Topic Pharmacological Actions of Drugs in the Brain: Exploring the Intricacies and Potential Therapeutic Applications View all 13 articles

Lutein inhibits glutamate-induced apoptosis in HT22 cells via the Nrf2/HO-1 signaling pathway

Provisionally accepted
Zhenhua Li Zhenhua Li 1Zhuohua Cao Zhuohua Cao 1Fangmei Chen Fangmei Chen 2Bin Li Bin Li 3,4*Hanyong Jin Hanyong Jin 1*
  • 1 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China, Yanji, China
  • 2 Institute of Science and Technology Information Research of Tibet Autonomous Region, Lhasa, 850008, China, Lhasa, China
  • 3 Department of Pharmacy, Key Laboratory of Pharmaceutical Research for Metabolic Diseases, Qingdao University of Science & Technology, Qingdao 266042, China, Qingdao, China
  • 4 Department of Medicament, College of Medicine, Tibet University, Lhasa 850000, China, Lhasa, China

The final, formatted version of the article will be published soon.

    Excessive glutamate levels induce oxidative stress, resulting in neuronal damage and cell death. While natural antioxidants show promise for neuroprotection, their effectiveness in the central nervous system (CNS) is limited by the blood-brain barrier. Lutein, a neuroprotective carotenoid, has gained attention for its ability to traverse this barrier and accumulate in various brain regions. However, the specific neuroprotective effects of lutein on hippocampal neurons have not been extensively explored before our investigation. This study aimed to elucidate the mechanisms underlying the protective effects of lutein against glutamate-induced cell death in HT22 cells. Our results demonstrate that lutein effectively attenuated glutamate-induced apoptosis due to its antioxidant properties. Additionally, lutein inhibited glutamate-induced mitochondrial-mediated apoptosis. We observed that lutein modulated the nuclear translocation of nuclear factor erythroid 2related factor 2 (Nrf2) and upregulated the expression of heme oxygenase-1 (HO-1). Inhibition of HO-1 by tin protoporphyrin (SnPP), a synthetic inhibitor, weakened the protective effect of lutein. Furthermore, we demonstrated that lutein prevented the aberrant activation of MAPKs induced by glutamate, including ERK1/2, p38, and JNK, thereby conferring oxidative protection. In conclusion, our study highlights the potent antioxidant properties of lutein, which effectively safeguards against glutamate-induced mitochondrial apoptotic cell death through the Nrf2/HO-1 signaling pathway and inhibition of MAPK activation. These findings demonstrate that lutein exerts a neuroprotective effect against glutamate-induced neuronal cell damage.

    Keywords: Lutein, Glutamate, neuroprotective effects, Oxidative Stress, Apoptosis

    Received: 15 May 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Li, Cao, Chen, Li and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Bin Li, Department of Pharmacy, Key Laboratory of Pharmaceutical Research for Metabolic Diseases, Qingdao University of Science & Technology, Qingdao 266042, China, Qingdao, China
    Hanyong Jin, Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China, Yanji, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.