Phenylethanoid glycosides derived from Cistanche deserticola promote neurological functions and the proliferation of neural stem cells for improving ischemic stroke

Jingjing Liu; Yanyan Wang; Qinyuan Li; Tao Liu; Xu Liu; Han Zhang; Zhifei Fu; Yifan Dai; Haiyuan Yang; Yu Wang; Ying Wang

doi:10.1016/j.biopha.2023.115507

Phenylethanoid glycosides derived from Cistanche deserticola promote neurological functions and the proliferation of neural stem cells for improving ischemic stroke

Biomed Pharmacother. 2023 Nov:167:115507. doi: 10.1016/j.biopha.2023.115507. Epub 2023 Sep 16.

Authors

Jingjing Liu¹, Yanyan Wang², Qinyuan Li¹, Tao Liu³, Xu Liu⁴, Han Zhang⁵, Zhifei Fu³, Yifan Dai⁶, Haiyuan Yang⁷, Yu Wang⁸, Ying Wang⁹

Affiliations

¹ Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China.
² School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
³ Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
⁴ Tianjin Xiqing District Hospital of Traditional Chinese Medicine, Tianjin, 300380, China.
⁵ Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; State Key Laboratory of Component based Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, 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; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
⁷ 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: hyyang@njmu.edu.cn.
⁸ School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; State Key Laboratory of Component based Chinese Medicine, Tianjin 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: wangyu@tjutcm.edu.cn.
⁹ 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: ywang@njmu.edu.cn.

PMID: 37722192
DOI: 10.1016/j.biopha.2023.115507

Abstract

Phenylethanoid glycosides derived from Cistanche deserticola (PhGs) are plant-derived natural medicinal compounds that occur in many medicinal plants. This study aims to investigate whether PhGs treatment improves the stroke and its potential mechanisms. Adult male C57BL/6 J mice were administrated PhGs once daily for 7 days after MCAO surgery. The neurological score, and catwalk were evaluated on Day 1, 3 and 7 after ischemic stroke. Furthermore, triphenyl-2,3,5-tetrazoliumchloride (TTC) and hematoxylin-eosin (H&E) staining were used for evaluating the infarct volume and neuronal restoration. The effects of PhGs on NSCs proliferation were investigated in vitro and in vivo. Western blot was used to detect the proteins of Wnt/β-catenin signaling pathway. This study found that PhGs effectively improved the neurological functions in ischemic stroke mice. TTC and H&E staining demonstrated that PhGs not only reduced infarct volume, but also improved neuronal restoration. The immunohistochemistry and 5-Ethynyl-2-deoxyuridine (EdU) incorporation assays revealed that PhGs promoted the proliferation of neural stem cells (NSCs) in subventricular zone (SVZ). In addition, transcriptome analysis of NSCs showed that the Wnt/β-catenin signaling pathway was involved in the PhGs induced NSCs proliferation. Importantly, the related proteins in the Wnt/β-catenin signaling pathway were changed after PhGs treatment, including β-catenin, Wnt3a, GSK-3β, c-Myc. PhGs treatment improved the stroke through enhancing endogenous NSCs proliferation via activating Wnt/β-catenin signaling pathway. Due to its effect on the proliferation of NSCs, PhGs are a potential adjuvant therapeutic drug for post-stroke treatment.

Keywords: Ischemic stroke; Neural stem cells; Phenylethanoid glycosides derived from Cistanche deserticola; Wnt signaling pathway.