Xu, Hao, Zhang, Huiyuan, Pop, Nona, Hall, Joe, Shazlee, Ibrahim, Wagner-Tsukamoto, Moritz, Chen, Zhiguo, Gu, Yuchun, Ma, Dan and Zhao, Chao (2024). The isoflavone puerarin promotes generation of human iPSC-derived pre-oligodendrocytes and enhances endogenous remyelination in rodent models. Journal of Neurochemistry ,
Abstract
Puerarin, a natural isoflavone, is commonly used as a Chinese herbal medicine for the treatment of various cardiovascular and neurological disorders. It has been found to be neuroprotective via TrK-PI3K/Akt pathway, which is associated with anti-inflammatory and antioxidant effects. Myelin damage in diseases such as in multiple sclerosis (MS) and ischemia induces activation of endogenous oligodendrocyte progenitor cells (OPC) and subsequent remyelination by newly formed oligodendrocytes. It has been shown that human induced pluripotent stem cells (hiPSC)-derived OPCs promote remyelination when transplanted to the brains of disease models. Here we ask whether and how puerarin is beneficial to the generation of hiPSC-derived OPCs and oligodendrocytes, and to the endogenous remyelination in mouse demyelination model. Our results show that puerarin increases the proportion of O4+ pre-oligodendrocytes differentiated from iPSC-derived neural stem cells. In vitro, puerarin increases proliferation of rat OPCs and enhanced mitochondrial activity. Treatment of puerarin at progenitor stage increases the yielding of differentiated oligodendrocytes. In rat organotypic brain slice culture, puerarin promotes both myelination and remyelination. In vivo, puerarin increases oligodendrocyte repopulation during remyelination in mouse spinal cord following lysolethicin-induced demyelination. Our findings suggest that puerarin promotes oligodendrocyte lineage progression and myelin repair, with a potential to be developed into therapeutic agent for neurological diseases associated with myelin damage.
Publication DOI: | https://doi.org/10.1111/JNC.16245 |
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Divisions: | College of Health & Life Sciences > Aston Medical School College of Health & Life Sciences College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG) Aston University (General) |
Funding Information: | This work was supported by Aston University to Dan Ma and Nona Pop (PhD) and by Royal Society\u2010Newton Advanced Fellowship to Zhiguo Chen and Chao Zhao (NA150482). We thank project support from Allife Medicine Science and Technology Ltd. (Beijing, Chin |
Additional Information: | Copyright © 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Uncontrolled Keywords: | Puerarin, hiPSC, oligodendrocyte progenitor cells, remyelination, mitochondria |
Publication ISSN: | 1471-4159 |
Data Access Statement: | The original data presented in the study are included in the article material; further inquiries can be directed to the corresponding<br/>authors. |
Last Modified: | 19 Nov 2024 18:07 |
Date Deposited: | 29 Oct 2024 16:14 |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) https://onlinel ... .1111/jnc.16245 (Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2024-10-18 |
Published Online Date: | 2024-10-18 |
Accepted Date: | 2024-09-30 |
Authors: |
Xu, Hao
Zhang, Huiyuan Pop, Nona Hall, Joe Shazlee, Ibrahim Wagner-Tsukamoto, Moritz Chen, Zhiguo Gu, Yuchun Ma, Dan ( 0000-0001-8628-8954) Zhao, Chao |