1. Academic Validation
  2. 6‴-Feruloylspinosin alleviates Aβ-induced toxicity by modulating relevant neurotransmitter and the AMPK/mTOR signaling pathway

6‴-Feruloylspinosin alleviates Aβ-induced toxicity by modulating relevant neurotransmitter and the AMPK/mTOR signaling pathway

  • Free Radic Biol Med. 2025 Feb 1:227:434-445. doi: 10.1016/j.freeradbiomed.2024.12.028.
Jinrui Liu 1 Yanqing Zhang 2 Mei Zhang 3 Qing Wang 3 Yuxin Pang 4 Junbo Xie 5
Affiliations

Affiliations

  • 1 College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 2 College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China. Electronic address: zhyqing@tjcu.edu.cn.
  • 3 College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, 300134, China.
  • 4 College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China. Electronic address: pyxmarx@126.com.
  • 5 School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: xiejb@tjutcm.edu.cn.
Abstract

Alzheimer's disease (AD) is a gradually progressive neurodegenerative disease with a serious impact on patients' quality of life. However, single-targeted therapies are not currently effective, and there is a need to find pluripotent drugs with multiple properties. This study aimed to characterize the metabolism of neurotransmitters using a targeted metabolomics approach and to identify the major metabolic pathways mainly affected by 6‴-feruloylspinosin (6-FS). The mechanism of action of 6-FS in the treatment of AD was elucidated based on experimental validation. The metabolomics analysis revealed changes in 13 metabolic profiles by the LC-MS/MS, with significant changes in five amino acid-related neurotransmitters identified primarily. Based on the correlations, we found an effect of mTOR inhibition on the above neurotransmitter metabolism. Furthermore, pretreatment with 6-FS activated the AMPK/mTOR signaling pathway, promoting cellular Autophagy, regulating oxidative stress homeostasis and inhibiting mitochondrial dysfunction. In short, these comprehensive analysis methods help clarify the preventive mechanism of 6-FS and potential targets in AD and provide the necessary support for developing Natural Products to prevent AD.

Keywords

6-FS; AMPK/mTOR pathway; Autophagy; Mitochondrial dysfunction; Neurotransmitter; Oxidative stress.

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