2. Academic Validation
  3. Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway

Parthenolide alleviates cognitive dysfunction and neurotoxicity via regulation of AMPK/GSK3β(Ser9)/Nrf2 signaling pathway

  • Biomed Pharmacother. 2023 Nov 21:169:115909. doi: 10.1016/j.biopha.2023.115909.
Jinfeng Sun 1,  Liwei Li 2,  Li Xiong 2,  Fan Chen 2,  Lingyu She 2,  Hao Tang 2,  Yuqing Zeng 2,  Ying Duan 3,  Luyao Li 2,  Wei Wang 4,  Gao Li 5,  Xia Zhao 6,  Guang Liang 7
Affiliations

Affiliations

  • 1 Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China.
  • 2 Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
  • 3 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China.
  • 4 Affiliated Yongkang First People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310012, China.
  • 5 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China. Electronic address: Gaoli@ybu.edu.cn.
  • 6 Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Affiliated Yongkang First People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310012, China. Electronic address: xiazhao@hmc.edu.cn.
  • 7 Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China; Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China. Electronic address: wzmcliangguang@163.com.
PMID: 37992573 DOI: 10.1016/j.biopha.2023.115909
Abstract

Alzheimer's disease (AD) stands as the predominant age-related neurodegenerative disorder, for which efficacious treatment remains elusive. An auspicious avenue for this disease lies in natural compounds sourced from tranditional medicine and plant origins. Parthenolide (PTN) is a natural product with multiple biological functionsand. Recent investigations have illuminated PTN's protective properties against neurological maladies; however, its potential therapeutic role against AD remains uncharted. This study aims to explore the role of PTN in treating AD. Our in vitro findings underscore PTN's bioactivity, as evidenced by its capacity to curtail Apoptosis, reduce Reactive Oxygen Species (ROS) production, and restore mitochondrial membrane potential in PC12 cells. Moreover, PTN treatment demonstrates a capacity to ameliorate deficits in spatial learning and memory in the 3 ×Tg-AD murine model. Notably, PTN's therapeutic efficacy surpasses that of a clinical agent, donepezil. Mechanistically, PTN's neuroprotective effects stem from its adept regulation of the AMPK/GSK3β(ser9)/Nrf2 signaling pathway and protection on neuronal cells from ROS-related Apoptosis. Although the molecular target and the pre-clinical evaluations of PTN need to be further explored, this study indicates PTN as a potential agent or lead compound for the drug development against AD.

Keywords

AMPK; Alzheimer’s disease; Cell apoptosis; Cognitive deficits; Parthenolide.

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