2. Academic Validation
  3. Alizarin attenuates oxidative stress-induced mitochondrial damage in vascular dementia rats by promoting TRPM2 ubiquitination and proteasomal degradation via Smurf2

Alizarin attenuates oxidative stress-induced mitochondrial damage in vascular dementia rats by promoting TRPM2 ubiquitination and proteasomal degradation via Smurf2

  • Phytomedicine. 2024 Oct 5:135:156119. doi: 10.1016/j.phymed.2024.156119.
Guo-Pin Pan 1,  Yan-Hua Liu 2,  Ming-Xu Qi 3,  Ya-Qi Guo 1,  Zhen-Lei Shao 2,  Hui-Ting Liu 1,  Yi-Wen Qian 4,  Shuang Guo 5,  Ya-Ling Yin 6,  Peng Li 7
Affiliations

Affiliations

  • 1 Henan international joint laboratory of cardiovascular remodeling and drug intervention, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China.
  • 2 Henan international joint laboratory of cardiovascular remodeling and drug intervention, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China; Pharmacy Department, the First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, China.
  • 3 College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130000, China.
  • 4 Department of Pharmacy, College of Basic Medicine and Forensic Medicien, Henan University of Science and Technology, Luoyang 471000, China.
  • 5 Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning 437100, China.
  • 6 Henan international joint laboratory of cardiovascular remodeling and drug intervention, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: yalingyin@xxmu.edu.cn.
  • 7 Henan international joint laboratory of cardiovascular remodeling and drug intervention, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: pengli@xxmu.edu.cn.
PMID: 39418971 DOI: 10.1016/j.phymed.2024.156119
Abstract

Background: Alizarin (AZ) is a natural anthraquinone with anti-inflammatory and moderate antioxidant properties.

Purpose: In this study, we characterized the role of AZ in a rat model of vascular dementia (VaD) and explored its underlying mechanisms.

Methods: VaD was induced by bilateral common carotid artery occlusion.

Results: We found that AZ attenuated oxidative stress and improved mitochondrial structure and function in VaD rats, which led to the improvement of their learning and memory function. Mechanistically, AZ reduced transient receptor potential melastatin 2 (TRPM2) expression and activation of the Janus-kinase and signal transducer activator of transcription (JAK-STAT) pathway in VaD rats. In particular, the reduction in the expression of TRPM2 channels was the key to the attenuation of the oxidative stress-induced mitochondrial damage, which may be achieved by increasing the expression of the E3 ubiquitin Ligase, Smad-ubiquitination regulatory factor 2 (Smurf2); thereby increasing the ubiquitination and degradation levels of TRPM2.

Conclusion: Our results suggest that AZ is an effective candidate drug for ameliorating VaD and provide new insights into the current clinical treatment of VaD.

Keywords

Alizarin; Oxidative stress; Smurf2; TRPM2; Ubiquitination; Vascular dementia.

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