2. Academic Validation
  3. Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death

Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death

  • Sci Rep. 2024 Apr 2;14(1):7707. doi: 10.1038/s41598-024-57824-2.
Wudtipong Vongthip 1 2,  Sunita Nilkhet 1 2,  Kanokkan Boonruang 2,  Monruedee Sukprasansap 3,  Tewin Tencomnao 4,  Seung Joon Baek 5
Affiliations

Affiliations

  • 1 Department of Clinical Chemistry, Faculty of Allied Health Sciences, Program in Clinical Biochemistry and Molecular Medicine, Chulalongkorn University, 10330, Bangkok, Thailand.
  • 2 Laboratory of Signal Transduction, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea.
  • 3 Food Toxicology Unit, Institute of Nutrition, Mahidol University, Nakhon Pathom, 73170, Thailand.
  • 4 Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand. tewin.t@chula.ac.th.
  • 5 Laboratory of Signal Transduction, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea. baeksj@snu.ac.kr.
PMID: 38565590 DOI: 10.1038/s41598-024-57824-2
Abstract

Neurodegenerative diseases, characterized by progressive neuronal dysfunction and loss, pose significant health challenges. Glutamate accumulation contributes to neuronal cell death in diseases such as Alzheimer's disease. This study investigates the neuroprotective potential of Albizia lebbeck leaf extract and its major constituent, luteolin, against glutamate-induced hippocampal neuronal cell death. Glutamate-treated HT-22 cells exhibited reduced viability, altered morphology, increased ROS, and Apoptosis, which were attenuated by pre-treatment with A. lebbeck extract and luteolin. Luteolin also restored mitochondrial function, decreased mitochondrial superoxide, and preserved mitochondrial morphology. Notably, we first found that luteolin inhibited the excessive process of Mitophagy via the inactivation of BNIP3L/NIX and inhibited lysosomal activity. Our study suggests that glutamate-induced autophagy-mediated cell death is attenuated by luteolin via activation of mTORC1. These findings highlight the potential of A. lebbeck as a neuroprotective agent, with luteolin inhibiting glutamate-induced neurotoxicity by regulating Autophagy and mitochondrial dynamics.

Keywords

Autophagy; Luteolin; Mitophagy; Neuroprotection; mTORC1 signaling pathway.

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