Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Discovery and validation of PURA as a transcription target of 20(S)-protopanaxadiol: Implications for the treatment of cognitive dysfunction

  • Feiyan Chen (Research and Innovation Center, College of Traditional Chinese Medicine.Integrated Chinese and Western Medicine College, Nanjing University of Chinese Medicine) ;
  • Wenjing Zhang (Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine) ;
  • Shuyi Xu (Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine) ;
  • Hantao Zhang (Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine) ;
  • Lin Chen (Department of Physiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine) ;
  • Cuihua Chen (Research and Innovation Center, College of Traditional Chinese Medicine.Integrated Chinese and Western Medicine College, Nanjing University of Chinese Medicine) ;
  • Zhu Zhu (Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine) ;
  • Yunan Zhao (Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine)
  • Received : 2023.01.09
  • Accepted : 2023.04.24
  • Published : 2023.09.01
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Abstract

Background: 20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown. Methods: In this study, we first used mass spectrometry-based drug affinity responsive target stability (DARTS) to identify the potential proteins of ginsenosides and intersected them with the transcription factor library. Second, the transcription factor PURA was confirmed as a target of PPD by biolayer interferometry (BLI) and molecular docking. Next, the effect of PPD on the transcriptional levels of target genes of PURA in brain tissues was determined by qRT-PCR. Finally, bioinformatics analysis was used to analyze the potential biological features of these target proteins. Results: The results showed three overlapping transcription factors between the proteomics of DARTS and transcription factor library. BLI analysis further showed that PPD had a higher direct interaction with PURA than parent ginsenosides. Subsequently, BLI kinetic analysis, molecular docking, and mutations in key amino acids of PURA indicated that PPD specifically bound to PURA. The results of qRT-PCR showed that PPD could increase the transcription levels of PURA target genes in brain. Finally, bioinformatics analysis showed that these target proteins were involved in learning and memory function. Conclusion: The above-mentioned findings indicate that PURA is a transcription target of PPD in brain, and PPD upregulate the transcription levels of target genes related to cognitive dysfunction by binding PURA, which could provide a chemical and biological basis for the study of treating cognitive impairment by targeting PURA.

Keywords

Acknowledgement

The study was financially supported by National Natural Science Foundation of China (No.82204647, 82003970), Supporting project of National Natural Youth Foundation of Nanjing University of Chinese Medicine (XPT82204647).

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