2. Academic Validation
  3. 2-Acetylacteoside improves recovery after ischemic stroke by promoting neurogenesis via the PI3K/Akt pathway

2-Acetylacteoside improves recovery after ischemic stroke by promoting neurogenesis via the PI3K/Akt pathway

  • Free Radic Biol Med. 2024 Nov 20:225:415-429. doi: 10.1016/j.freeradbiomed.2024.10.268.
Meng Wang 1,  Songyu Xing 1,  Yang Liu 2,  Zongren An 2,  Xu Liu 3,  Tao Liu 4,  Han Zhang 4,  Yifan Dai 5,  Haiyuan Yang 6,  Yu Wang 7,  Ying Wang 8
Affiliations

Affiliations

  • 1 Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China.
  • 2 ICU, Nanjing Gaochun People's Hospital, 53 Maoshan Road, Gaochun District, Nanjing, 211300, China.
  • 3 Qilu Medical University, Shandong, 255300, China.
  • 4 Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 5 Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China.
  • 6 Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China. Electronic address: [email protected].
  • 7 School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: [email protected].
  • 8 Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China; Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 211166, China. Electronic address: [email protected].
PMID: 39396583 DOI: 10.1016/j.freeradbiomed.2024.10.268
Abstract

Ischemic stroke induces adult neurogenesis in the subventricular zone (SVZ), even in elderly patients. Harnessing of this neuroregenerative response presents the therapeutic potential for post-stroke recovery. We found that phenylethanoid glycosides (PhGs) derived from Cistanche deserticola aid neural repair after stroke by promoting neurogenesis. Among these, 2-acetylacteoside had the most potent on the proliferation of neural stem cells (NSCs) in vitro. Furthermore, 2-acetylacteoside was shown to alleviate neural dysfunction by increase neurogenesis both in vivo and in vitro. RNA-sequencing analysis highlighted differentially expressed genes within the PI3K/Akt signaling pathway. The candidate target Akt was validated as being regulated by 2-acetylacteoside, which, in turn, enhanced the proliferation and differentiation of cultured NSCs after oxygen-glucose deprivation/reoxygenation (OGD/R), as evidenced by Western blot analysis. Subsequent analysis using cultured NSCs from adult subventricular zones (SVZ) confirmed that 2-acetylacteoside enhanced the expression of phosphorylated Akt (p-Akt), and its effect on NSC neurogenesis was shown to be dependent on the PI3K/Akt pathway. In summary, our findings elucidate for the first time the role of 2-acetylacteoside in enhancing neurological recovery, primarily by promoting neurogenesis via Akt activation following ischemic brain injury, which offers a novel strategy for long-term cerebrological recovery in ischemic stroke.

Keywords

2-Acetylacteoside; Akt; Cerebrological recovery; Ischemic stroke; NSCs; Neurogenesis.

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