Zhi Zhang1,2 · Xin Shu1,2 · Qian Cao1,2 · Lushan Xu1,2 · Zibu Wang1,2 · Chenggang Li1,2 · Shengnan Xia2,3 · Pengfei Shao2,3 · Xinyu Bao2,3 · Liang Sun1,2 · Yuhao Xu2,3 · Yun Xu1,2,3,4,51 Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China
2 Department of Neurology, Nanjing Drum Tower Hospital, Afliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing 210008, China
3 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China
4 Jiangsu Provincial Key Discipline of Neurology, Nanjing 210008, China 5 Nanjing Neurology Medical Center, Nanjing 210008, China
Abstract
Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Keywords
Honokiol; White matter injury; Oligodendrocyte; Vascular dementia
